Studies on human retroviruses and oncogenes have been pursued with particular emphasis on their role in human disease. Two subgroups of a human T-cell leukemia virus, designated HTLV-I and HTLV-II, have the unique capacity to transform human T cells in vitro, leading to cloned cell populations. Molecular cloning and comparative analysis of the genomes of HTLV-I and HTLV-II revealed sequence conservation throughout but particularly in a coding region designated tat and in enhancer sequences in the viral LTR. These results have direct relevance in the possible mechanism of transformation by these viruses. Recently HTLV-III has been postulated to be the etiologic agent of acquired immune deficiency syndrome. We have molecular cloned and sequenced the HTLV-III genomes. A comparative analysis of the multiple HTLV-III isolates has shown divergence in the env gene. HTLV-III has been found to be similar to LAV or ARV and shows sequence homology to visna virus. HTLV-III infection has also been found in brain tissues of AIDS patients with encephalopathy. This was made possible by the recently developed in situ hybridization technique. It is now possible to express various HTLV-III proteins in prokaryotic systems and show transfection of biologically active HTLV-III DNA and demonstration of cytopathic effect.