The measurement of hormones in saliva: possibilities and pitfalls

The easy stress-free, non-invasive nature of saliva collection makes it one of the most accessible body fluids and it is potentially of value in studying normal human physiology as well as pathology. Measurements of salivary hormone levels will usually only be of value if they reflect the plasma level of the hormone and the relationship between the saliva and plasma levels of many hormones have been studied by a number of groups. The measurement of the salivary level is a valuable clinical tool for some hormones (e.g. cortisol, oestriol, progesterone), is of little value for others (e.g. cortisone, dehydroepiandrosterone sulphate, thyroxine, pituitary hormones) and for many others the saliva/plasma relationship is not yet sufficiently understood to assess the value of the salivary measurement. As well as reviewing the state of our knowledge of the salivary concentration of many hormones this review outlines a number of "rules of thumb" concerning the presence of hormones in saliva, their saliva/plasma relationship and the potential usefulness of assays of their salivary concentration.     

The monitoring of the menstrual status of female athletes by salivary steroid determination and ultrasonography

This study was designed to evaluate whether traditional plasma hormone determinations can be adequately replaced by measurements of salivary hormones. Eleven young sportswomen with menstrual irregularities attributed to strenuous physical exercise participated in this study. Mean body weight expressed as a percentage of ideal body weight was 92%, SD 4%. Their mean weekly training distance was 35 km, SD 15. Basal plasma endocrinological measurements revealed a hypo-oestrogenic status (mean plasma oestradiol values: 22 pg.ml-1, SD 8.8), and a deficient luteal phase (mean plasma progesterone: 2.9 ng.ml-1, SD 2.1). Pre-exercise salivary sex steroids were low. Salivary progesterone levels were 39.3 pg.ml-1, SD 9.5 (normal ranges in saliva: 25-60 pg.ml-1), salivary oestrone (E1) was 12.2 pg.ml-1, SD 2.3 (normal ranges in saliva: 7.5-25 pg.ml-1), and salivary oestradiol (E2) less than 1.9 pg.ml-1, SD 1.1 (normally 1.0-10.0 pg.ml-1). After a 21-km run, all salivary steroids appeared to increase. Mean salivary testosterone levels increased by 15.2% and salivary progesterone by 14.8%. Mean salivary oestrogens also increased (E1: +13.9%; E2: +21.1%). These findings confirm the results of earlier studies which found higher post-exercise plasma sex steroid levels. Since salivary measurements are believed to reflect non-protein-bound, thus free steroid levels, the results obtained by these techniques may provide a more realistic picture of the hormonal effects of physical exercise. In future, more accurate, cost-effective and easier techniques for salivary measurements may offer additional advantages.     

Bioluminescence immunoassay for cortisol using recombinant aequorin as a label

The analysis of hormones in saliva is a powerful tool in the assessment of a patient's endocrine function, since it allows multiple noninvasive samplings. Since salivary levels of most hormones are 10 to 50 times lower than plasma levels, accurate and highly sensitive assays are needed for saliva measurements. Herein, we describe the development of a solid-phase competitive immunoassay for cortisol in saliva, in which a mutant of the photoprotein aequorin has been used as a label. We have chemically conjugated cortisol to aequorin at different molar ratios. The various cortisol-aequorin conjugates were characterized in terms of bioluminescent activity and affinity for the anti-cortisol antibody. The conjugate that gave the best analytical performance was used for the development of the immunoassay and the analysis of cortisol in saliva samples. The conjugates were stable for at least 6 months when stored at 4 degrees C. The method fulfilled all the standard requirements of precision and accuracy. The optimized immunoassay gave a detection limit of 300 fmol/tube, corresponding to 3 nmol/L, with a linear dynamic range of 10-1000 nmol/L. Therefore, cortisol can be detected down to 0.1 ng in 100 microl of saliva sample using this assay, without any sample pretreatment. This detection limit is almost one order of magnitude lower than the physiological levels of salivary cortisol, which are reported to be 10-25 nmol/L. This allows the quantification of salivary cortisol to be performed in the linear range of the calibration curve, which is most reliable for quantification purposes.     

Progesterone metabolism in human saliva in vitro.

Human salivary glands are known to be able to metabolize progesterone as well as other steroid hormones. The rate of progesterone metabolism in the salivary glands is so low that it is not thought to affect salivary progesterone concentrations. On the other hand it is usually recommended that saliva should be frozen quickly after the collection to prevent any kind of metabolism in saliva. When saliva is collected at home e.g. delayed freezing or partial thawing during to transport to laboratory may create circumstances where progesterone metabolism may occur. However, it is not known to which extent progesterone metabolism continues in saliva and whether this continued metabolism of progesterone affects salivary hormone levels. Paraffin-stimulated salivary samples were collected from female (N = 6) and male (N = 6) dental students and perimenopausal women (N = 8). The salivary samples were incubated with 14C-progesterone for 2 h at 37 degrees C in a shaking water bath. Metabolites were analyzed using thin-layer chromatography and autoradiography and quantified by liquid scintillation counting. Human saliva was found to be able to metabolize progesterone, but its metabolic activity was very low, 9.3 and 6.8 pmol/ml/h in young adults and perimenopausal women, respectively. Metabolic activity was higher in whole saliva than in the corresponding activities of the supernatant or sonicated fraction of the same saliva. The supernatant fraction, which was thought to be mainly representative of glandular saliva, was metabolically least active. The polar metabolites of progesterone predominated in all incubations. The metabolic activity of saliva is probably mainly due to its cellular content and the contribution of this activity to salivary progesterone concentrations is not significant.     

Validation of a cortisol enzyme immunoassay and characterization of salivary cortisol circadian rhythm in chimpanzees (Pan troglodytes)

Monitoring concentrations of stress hormones is an important tool for behavioral research and conservation for animals both in the wild and captivity. Glucocorticoids can be measured in mammals as an indicator of stress by analyzing blood, feces, urine, hair, feathers, or saliva. The advantages of using saliva for measuring cortisol concentrations are three-fold: it is minimally invasive, multiple samples can be collected from the same individual in a short timeframe, and cortisol has a relatively short response time in saliva as compared with other materials. The purpose of this study was to: (1) conduct an adrenocorticotropic hormone (ACTH) challenge as a physiological validation for an enzyme immunoassay to measure salivary cortisol in chimpanzees and (2) characterize the circadian rhythm of salivary cortisol in chimpanzees. We determined that salivary cortisol concentrations peaked 45 min following the ACTH challenge, which is similar to humans. Also, salivary cortisol concentrations peaked early in the morning and decreased throughout the day. We recommend that saliva collection may be the most effective method of measuring stress reactivity and has the potential to complement behavioral, cognitive, physiological, and welfare studies.     

Changes in adrenal and testicular activity monitored by salivary sampling in males throughout marathon runs

Measurement of cortisol and testosterone in saliva samples provided by marathon runners at 6.4 km (4-mile) intervals has been used for monitoring acute changes in adrenal and testicular activity, and the changes compared with mean values in timed samples on five rest days. The collection of mixed whole saliva was well accepted; the missed sample rate in the 8 runners in the Cardiff marathon was less than 10%. On rest days, salivary cortisol and testosterone were within the normal male range and showed a circadian rhythm; mean values at 08.00 h (23.5 nmol L-1; 258 pmol L-1, p less than 0.001, p less than 0.001 respectively) were higher than at 22.00 h (2.8 nmol L-1; 130 pmol L-1). In samples collected at 09.00 h, immediately prior to the Cardiff marathon, cortisol (25.1 nmol L-1) and testosterone (304 pmol L-1) were higher than the mean values (14.9 nmol L-1; 209 pmol L-1) on non-run days. Concentrations of both steroids increased during the marathon; testosterone peaked (442 pmol L-1) at 21 miles, whereas cortisol continued to increase, being maximal (87.9 nmol L-1) at 30 min after completion of the run. Four of the runners in the Cardiff marathon also participated in the Bristol marathon and the changing patterns in salivary hormones were strictly comparable. Salivary sampling would appear to be of value in monitoring acute and rhythmic changes in endocrine function in marathon runners. The temporal relationship between changes in salivary cortisol and testosterone are consistent with direct inhibition of testicular secretion by high cortisol concentrations.     

Validation of salivary cortisol and testosterone assays in chimpanzees by liquid chromatography‐tandem mass spectrometry

Owing to its high temporal sensitivity, saliva has distinct advantages for measuring steroids, compared with other noninvasive samples such as urine and feces. Here, we report the validity of assaying salivary cortisol (C) and testosterone (T) using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) in captive male chimpanzees, Pan troglodytes. For both the C and T concentrations, we found positive relationships between saliva and plasma. The concentrations of C and T in saliva showed clear patterns of diurnal fluctuation, whereas those in urine and feces did not. These results suggest that the salivary steroid concentrations can be regarded as good indicators of circulating steroid levels. We also developed and validated an efficient method for collecting saliva samples from cotton rope. Although rope includes inherent steroid‐like compounds and may affect the accuracy of steroid measurements, our rope‐washing procedures effectively removed intrinsic steroidal materials. There was a significant association between the C and T concentrations measured from saliva collected from rope licked by the chimpanzees and those measured from saliva collected directly from the mouth. Salivary T values estimated by LC/MS‐MS were similar to those measured by radioimmunoassay. The results indicate the usefulness of saliva as a noninvasive steroid measure and that steroids in the saliva of chimpanzees can be accurately measured by LC‐MS/MS. Am. J. Primatol. 71:696–706, 2009. © 2009 Wiley‐Liss, Inc.     

The physiological role of hormones in saliva

The assessment of hormones in saliva has gained wide acceptance in clinical endocrinology. To date, there is no hypothesis as to why some hormones can be found in saliva, while others cannot, and whether there is a physiological consequence of this fact. A number of carefully performed studies give examples of important physiological hormonal activity in saliva. Steroids, such as androgens, act as pheromones in olfactory communication of various mammalian species, such as facilitating mating behavior in swine or serving as odor cues for rodent nestlings. Salivary peptide hormones, such as epidermal growth factor (EGF) and transforming growth factor‐α (TGF‐α), and amines such as melatonin, are involved in the regulation of inflammatory processes and in the promotion of cell proliferation, and contribute to a rapid wound healing in the oropharyngeal epithelia. Current data provide evidence of the involvement of salivary cytokines, such as interleukin‐8 and leptin, in tumorgenesis in the oral cavity and the salivary glands. The tumor tissues express and release significantly more of these cytokines than healthy glands. Consequently, the assessment of salivary hormone profiles may provide promising targets for diagnostic tumor markers.     

The scientific exploration of saliva in the post-proteomic era: from database back to basic function

The proteome of human saliva can be considered as being essentially completed. Diagnostic markers for a number of diseases have been identified among salivary proteins and peptides, taking advantage of saliva as an easy-to-obtain biological fluid. Yet, the majority of disease markers identified so far are serum components and not intrinsic proteins produced by the salivary glands. Furthermore, despite the fact that saliva is essential for protecting the oral integuments and dentition, little progress has been made in finding risk predictors in the salivary proteome for dental caries or periodontal disease. Since salivary proteins, and in particular the attached glycans, play an important role in interactions with the microbial world, the salivary glycoproteome and other post-translational modifications of salivary proteins need to be studied. Risk markers for microbial diseases, including dental caries, are likely to be discovered among the highly glycosylated major protein species in saliva. This review will attempt to raise new ideas and also point to under-researched areas that may hold promise for future applicability in oral diagnostics and prediction of oral disease.     

Quantifying blood leakage into the oral mucosa and its effects on the measurement of cortisol, dehydroepiandrosterone, and testosterone in saliva

The impact of blood leakage due to microinjury to the oral cavity on the measurement of salivary hormones was examined. Saliva samples were collected before, immediately after, and then every 15 min for 1 h following vigorous tooth brushing. Blood in saliva was quantified by visual inspection of discoloration, Hemastix reagent strips to detect hemoglobin, and an immunoassay for transferrin. The presence of blood in saliva immediately after microinjury was confirmed by all methods. Hemoglobin and transferrin levels remained elevated over baseline for at least 30 min. Levels of salivary testosterone increased over baseline and remained elevated for 30 min in response to microinjury. Microinjury induced change in salivary testosterone was more closely associated with the change in transferrin than hemoglobin levels or discoloration ratings. On average, levels of salivary dehydroepiandrosterone (DHEA) did not increase in response to microinjury. However, individual differences in microinjury induced change in DHEA were associated with discoloration ratings. Salivary cortisol levels, on average, were neither responsive to microinjury, nor were individual differences in cortisol change associated with blood contamination measures. Neither diurnal nor gender-related differences in baseline hormone levels predicted the impact of blood leakage on quantitative salivary measurements. The findings suggest ecologically valid minor-to-moderate level microinjuries to the oral cavity have negligible effects on the measurement of salivary cortisol, but may be important to quantify and control when assessing other hormones especially testosterone.     

Influence of commercial collection devices for saliva on the reliability of salivary steroids analysis

Saliva analysis is an accepted non-invasive alternative to plasma in pediatric endocrinology. Although commercial saliva collectors are available, the reliability of these devices for the analysis of salivary hormones has not been proved. We investigated the recovery and linearity of salivary steroids (cortisol, cortisone, 17-hyroxyprogesterone, testosterone, androstenedione) being relevant in endocrine research and therapy control. Pooled saliva was spiked with ascending concentrations of the steroids and applied onto a variety of absorbents, such as the cotton and the polyester (PE) Salivette (Sarstedt), the foam-tip applicator (Whatman) and strips of blood-spot collection paper (Whatman). Analysis was performed by LC-MS/MS. Best results were achieved using the PE Salivette, yielding recoveries (%) of 99.8 (cortisol), 98.7 (cortisone), 91.8 (17OHP), 96.3 (testosterone), 98.9 (androstendione) with a volume recovery of 98+/-1%. Using the blood-spot paper, recoveries (%) were 92.0 (cortisol), 89.1 (cortisone), 72.0 (17OHP), 70.3 (testosterone) and 77.1 (androstendione). The recovery of glucocorticoids was significantly higher compared to androgens (p<0.001). The recovery of liquid volume was 95+/-2%. The cotton Salivette yielded weak recoveries of 88.7 (cortisol), 86.2 (cortisone), 60.9 (17OHP), 62.0 (testosterone) and 72.4 (androstendione). The recovery of the glucocorticoids differed significantly from the androgens (p<0.001). Liquid recovery was most variable with 89+/-8%. The weakest recoveries were found in the foam-tips being 76.2 for cortisol, only 41.8 for cortisone, 31.1 for 17OHP, 38.5 for testosterone and 36.1 for androstendione. The volume recovery here was 97+/-1%. We assume only the PE version of the Salivette suitable for salivary steroid analysis. The weak recovery from the cotton version is a severe problem due to lacking comparability with values obtained with the polyester wads and the weak homogeneity as observed over a physiological concentration range.     

Die rolle der speichelsekrete im wechselverhaltnis zwischen tier und Nahrungspflanze bei homopteren und heteropteren

Zusammenfassung Im Speichel der Rhynchoten gibt es verschiedene Verdauungsenzyme, die eine weitgehende Anpassung hinsichtlich der Art der Nahrung aufweisen und bei der Verdauung wichtig sind. Zugleich gibt es im Rhynchotenspeichel auch Pflanzenwuchs hemmende Stoffe Auxine und Viren, die alle Krankheitszustände bei den Nahrungspflanzen verursachen welche ihrerseits die Lebensbedingungen der Schädlinge fördern.

---

Summary The above article is a short survey of the relation between the salivary secretions of the Hemiptera and their host plants.In analyses of the composition secretions in the salivary glands of phytophagous Homoptera and Heteroptera, the most extensive work has been done on the digestive enzymes. Proteases, amylases, saccharase, maltase, pectinase and lipase have been detected, but most commonly only 2–3 of these occurs in any one species. An adaptation of the enzyme complement to the diet is evident and in this respect the feeding site used by the insect is especially decisive to the enzyme composition of the saliva. Proteases and amylases occur in the saliva of mesophyll feeders, but are absent in phloem feeders, for which they are useless because, from the insect's point of view, the food is already digested. The adaptation of the salivary enzymes to the nature of the food seems to be largely inherited for a diet containing nothing but sucrose does not induce adaptive changes in the enzyme content of the salivary glands. By contrast, papain seems to be transferred from a synthetic food to the salivary glands.The disease symptoms caused in plants by the salivary toxins of Homoptera and Heteroptera have many similarities to those caused by abnormal amounts of growth hormones. Indole-tri-acetic acid has been detected in extracts of crushed aphids and leafhoppers, although no growth stimulating hormones have been detected in salivary glands dissected from several heteropterous bugs and one aphid. On the contrary, substances inhibiting plant growth exist in the salivary glands of many Heteroptera and in at least one aphid. In some experiments with a heteropterous bug, indole-triacetic was observed to have been transferred from a synthetic diet to the salivary glands. It seems possible that auxins, enzymes and other phytotoxic substances occurring in the salivary glands of insects may at last in some cases originate from the host plant and are not produced by the insect.The salivary enzymes without doubt play an important role in the digestion of the insects secreting them. They are important also in the differentation of Homoptera and Heteroptera to different modes of life. The auxins or auxin inhibitors, as wel as all phytotoxic substances in the salivary glands of Homoptera and Heteroptera are significant for these animals by changing the physiological state of the host plant in such a direction that its suitability as a source of food increases.

     

Saliva proteomics as an emerging, non-invasive tool to study livestock physiology, nutrition and diseases

Saliva is an extraordinary fluid in terms of research and diagnostic possibilities. Its composition in electrolytes, hormones and especially its proteome contains information about feeding status, nutritional requirements and adaptations to diet and environment, and also about health status of animals. It is easy to collect on a non-invasive and routine basis without any need for special training. Therefore, the analysis of salivary proteomes is going to emerge into a field of high interest with the future goal to maintain and improve livestock productivity and welfare. Moreover, the comprehensive analysis and identification of salivary proteins and peptides in whole and glandular saliva is a necessary pre-requisite to identify animal disease biomarkers and a powerful tool to better understand animal physiology. This review focuses on the different approaches used to study the salivary proteomes of farm animals, in respect to the physiology of nutrition and food perception in relation to food choices. The potential of animal saliva as a source of disease biomarkers will also be pointed out. Special emphasis is laid on the 'ruminating triad' - cattle, goat and sheep - as well as swine as major species of animal production in Western and Southern Europe.     

Proteomics and its applications for biomarker discovery in human saliva

Human saliva is a biological fluid with enormous diagnostic potential. Because saliva can be non-invasively collected, it provides an attractive alternative for blood, serum or plasma. It has been postulated that the blood concentrations of many components are reflected in saliva. Saliva harbors a wide array of proteins, which can be informative for the detection of diseases. Profiling the proteins in saliva over the course of disease progression could reveal potential biomarkers indicative of different stages of diseases, which may be useful in medical diagnostics. With advanced instrumentation and developed refined analytical techniques, proteomics is widely envisioned as a useful and powerful approach for salivary proteomic biomarker discovery. As proteomic technologies continue to mature, salivary proteomics have great potential for biomarker research and clinical applications. The progress and current status of salivary proteomics and its application in the biomarker discovery of oral and systematic diseases will be reviewed. The scientific and clinical challenges underlying this approach will also be discussed.     

Proteomics and its applications for biomarker discovery in human saliva

Human saliva is a biological fluid with enormous diagnostic potential. Because saliva can be non-invasively collected, it provides an attractive alternative for blood, serum or plasma. It has been postulated that the blood concentrations of many components are reflected in saliva. Saliva harbors a wide array of proteins, which can be informative for the detection of diseases. Profiling the proteins in saliva over the course of disease progression could reveal potential biomarkers indicative of different stages of diseases, which may be useful in medical diagnostics. With advanced instrumentation and developed refined analytical techniques, proteomics is widely envisioned as a useful and powerful approach for salivary proteomic biomarker discovery. As proteomic technologies continue to mature, salivary proteomics have great potential for biomarker research and clinical applications. The progress and current status of salivary proteomics and its application in the biomarker discovery of oral and systematic diseases will be reviewed. The scientific and clinical challenges underlying this approach will also be discussed.     

唾液成分在刺吸式昆虫与植物关系中的作用

近年来,人们对刺吸式昆虫唾液成分的研究,揭示出其在刺吸式昆虫与植物关系中的重要作用。对多数刺吸式昆虫而言,他们取食时会分泌胶状和水状两种唾液,其中胶状唾液会在取食早期分泌形成唾液鞘来围绕并保护口针,通过直接和间接的作用来帮助取食;而水状唾液中则包含了果胶酶、纤维素酶、多酚氧化酶、过氧化物酶、碱性磷酸酯酶、蔗糖酶等组分,来帮助刺吸式昆虫对植物穿刺、消化食物、解毒次生物质并破坏植物的防御反应。有趣的是,唾液成分同时还可以诱导植物的防御反应,包括诱导植物的伤信号引起直接防御反应和诱导植物产生挥发物吸引植食者的天敌引起间接防御反应。并且,许多刺吸式昆虫取 食能够特异性地引发植物的病理反应,有研究推测刺吸式昆虫唾液中多聚半乳糖醛酸酶、碱性磷酸酯酶、蔗糖酶、多酚氧化酶等成分可能是某些植物特定病理反应的激发子,但是目前还没有定论,同时许多刺吸式昆虫唾液中的氨基酸和蛋白酶还是引起植物虫瘿的原因之一。 迄今的研究表明,刺吸式昆虫会根据不同的寄主植物和不同的生理需要,通过唾液组分的改变,来达到取食和发育的目的。对刺吸式昆虫唾液成分和作用机理的研究,可以为揭示刺吸式昆虫致害机理特别是传毒机理、指导害虫有效治理、阐明其与植物的协同进化等提供一定的思路。     

Salivary concentration of progesterone and cortisol significantly differs across individuals after correcting for blood hormone values

Between‐individual variation of salivary progesterone (P4) and cortisol levels does not always closely reflect blood hormone concentrations. This may be partly a function of individual differences in salivary hormone excretion. We tested whether time of day at sampling and ethnicity contributed to individual variation in salivary hormones after adjusting for blood hormone levels. Forty‐three Caucasian and 15 Japanese women (18–34 years) collected four sets of matched dried blood spot (DBS) and saliva specimens across a menstrual cycle (N = 232 specimen sets). Linear fixed‐effects (LFE) models were used to estimate the effects of diurnal variation and ethnicity on salivary P4 and cortisol while adjusting for DBS levels. For each hormone, women with exclusively positive or negative residuals (unexplained variance) from the LFE models were categorized as high‐ or low‐saliva‐to‐DBS hormone ratio (SDR; high or low salivary secretors), respectively. We found that salivary P4 (P < 0.05) was significantly higher in early morning compared to the afternoon, after controlling for DBS levels, ethnicity, and BMI. After further adjusting for this diurnal effect, significant individual variation in salivary P4 and cortisol remained: sixteen and nine women, respectively were categorized as low or high salivary secretors for both hormones (P < 0.001), suggesting systematic individual‐specific variation of salivary hormonal concentration. We conclude that when saliva is used to quantify P4 or cortisol levels, time of day at sampling should be controlled. Even with this adjustment, salivary P4 and cortisol do not closely mirror between‐ individual variation of serum P4 and cortisol in a substantial proportion of individuals. Am J Phys Anthropol 149:231–241, 2012. © 2012 Wiley Periodicals, Inc.     

Effect of chewing betel nut on measurements of salivary progesterone and estradiol

The measurement of steroids in saliva is both simple and non-invasive and has been widely used in field and clinical-based research. The observance of particular cultural practices by some populations, however, may hamper accurate hormonal analyses. The present study evaluated the effects of one such practice-the chewing of betel nut-on the accurate measurement of salivary progesterone and estradiol. A time series experiment was conducted among Bangladeshi women who are regular users of betel nut. Salivary steroids were analyzed by radioimmunoassay in samples collected prior to and then 30, 60, 120, and 240 min following betel quid use. Results show no significant difference between basal steroid levels and those obtained 60, 120, and 240 min after chewing betel nut. We conclude that with specific collection protocols that take into account time since chewing, salivary steroid analyses can be undertaken in populations among whom the practice of chewing betel nut is endemic.     

Analysis of paraprotein transport into the saliva by using anti-idiotype antibodies

To determine the extent of clonal involvement of the secretory immune system and the origin of salivary immunoglobulins (Ig) in monoclonal gammopathy patients, saliva and serum samples were collected from five affected individuals (two IgA myelomas, one IgG myeloma, one IgG benign monoclonal gammopathy, and one IgM lymphoma) and were assayed for the presence of monoclonal Ig. Purified polyclonal or monoclonal anti-idiotype (Id) antibodies were prepared against each of the isolated serum paraproteins. In all five individuals, the patient saliva samples inhibited the binding of 125I-labeled homologous Ig to the corresponding anti-Id antibodies, but normal saliva did not. The concentration of Id in patients' saliva varied from 1 to 400 micrograms/ml; i.e., 0.004 to 1.0% of the corresponding serum values. Saliva of a lymphoma patient whose IgM kappa protein exhibited rheumatoid factor (RF) activity also contained RF. The salivary Id-bearing molecules were found to have the same Ig isotype as the serum paraproteins. The myeloma IgA represented a minor component (0.4 and 3.9%) of the total salivary IgA. The salivary IgA myeloma proteins were associated at least in part with secretory component, but the salivary IgG paraproteins were not. In an IgA myeloma patient, a minority (17%) of the IgA+ plasma cells found in the lacrymal gland biopsy specimen were Id+, whereas the great majority (98%) of bone marrow IgA plasma cells were Id+. The results suggest active transport rather than passive transudation of myeloma IgA into the patients' saliva, and the integrity of the secretory immune system was not compromised by the neoplastic process.