PIP: Several converging lines of research have linked a human T-cell lymphotropic retrovirus, human T-lymphotropic virus type III (HTLV-III), to the pathogenesis of acquired immunodeficiency syndrome (AIDS). This article traces the basic research that led to this finding and outlines possible clinical implications of this new information. Cultured cells derived from US patients with T-cell growth factor receptive positive T-cell lymphoproliferative disease were the source of the 1st isolates of human retroviruses in 1978-80. It then became apparent that HTLV should be viewed as a family of related T-cell lymphotropic retroviruses. The prototypical member of the family is referred to as HTLV-I, while the 2nd member is designated HTLV-II. HTLV-I has no common pattern of chromosomal integration, yet can transform normal T cells in vitro, suggesting that there is a trans mechanism for the leukomogenic effect of this virus. All members of the HTLV family are exogenous viruses isolated from mature T cells, infect mature T cells in vitro, have a reverse transciptase with similar biochemical features, possess some cross-reacting antigens, have major core proteins of similar size, exhibit some homology in nucleotide sequence, have a pX sequence at the 3' end of the genome, and induce formation of multinucleated giant cells upon in vitro infection of some T cells. Knowledge of HTLV-III is expected to affect many phases of basic research with clinical implications. 1st, there are new possibilities for identifying early cases of AIDS through antibody testing. 2nd, the discovery of an immunosuppressive retrovirus in AIDS could serve as a stimulus to re-examine endemic forms of cancer in Third World countries. 3rd, the identification of HTLV-III makes it possible to study the effect of more than 1 retrovirus in a given patient. 4th, current technology may make it possible to begin formulating rational interventions directed against a cause rather than the manifestations of AIDS.