Abstract: Human immunodeficiency virus type 1 (HIV-1) isolates are classified phenotyically into syncytium-inducing (SI) and non-syncytium-inducing (NSI) according to their capacity to induce syncytia in MT-2 cells.Strains of HIV-1 are also classified based on their co-receptor usage.Viruses using the seven-transmembrane,G-protein-coupled,chemokine receptor CCR5,CXCR4,or both are termed R5,X4,and R5X4,respectively.HIV-1 strains of SI and X4 appear to have identical biological properties such as replication rate,cell tropism,and syncytium-inducing capacity.NSI and R5 viruses also show identical biological properties.The phenotypes of HIV-1 influence and determine viral transmission,pathogenesis and disease progression.In the course of HIV-1 infection,disease progression is associated with a switch in viral phenotype from NSI to SI,and a change in co-receptor usage from CCR5 to CXCR4.The V3 domain of HIV-1 gpl20,specifically,amino acids at V3 position 11 and 25,play a dominant role in determinant of viral phenotype and co-receptor usage.V3 sequences provide important information for prediction of HIV-1 phenotype and disease progression using bioinformatics approaches.