A cohort of homosexual men at high risk of the acquired immunodeficiency syndrome (AIDS) was monitored to examine the relation between lifestyle, clinical conditions, T-lymphocyte subsets, and antibody to the AIDS-associated human retrovirus, human T-cell leukaemia virus III (HTLV-III). HTLV-III antibodies were present in 35 (53%) of the 66 subjects tested in June, 1982. 4 of the seronegative subjects had HTLV-III antibodies when re-tested one year later, a seroconversion rate of 1.2% per month. In the HTLV-III seropositive subjects, AIDS developed at a rate of 6.9% per year (minimum incidence of AIDS = 4.6% per year) and other clinical signs of immunodeficiency (lesser AIDS) at 13.1% per year. All 6 of the AIDS cases and at least 8 of the 10 lesser AIDS cases had detectable HTLV-III antibodies 1 week to 21 months before diagnosis. Of 24 other subjects with stable lymphadenopathy, 19 (79%) had or acquired HTLV-III antibodies. Lower helper T-cell counts were very closely related to HTLV-III seropositivity (r = -0.53, p = 0.0001), even in the 26 healthy subjects with no clinical abnormalities (r = -0.37, p = 0.07). In both univariate and multivariate analyses, the lifestyle risk factors for HTLV-III seropositivity were large number of homosexual partners (p less than or equal to 0.03) and receptive anal intercourse (p less than or equal to 0.03), with an apparent synergistic interaction between these two activities (chi 2 = 8.71, p = 0.003). These data suggest that frequent receptive anal intercourse with many homosexual partners predisposes to HTLV-III infection with the consequent emergence of lymphadenopathy and the various manifestations of lesser and fully fledged AIDS.