A cohort of 6875 homosexual men, initially seen at the San Francisco City Clinic between 1978 and 1980, were studied to determine the incidence and prevalence of the acquired immunodeficiency syndrome, related conditions, and infection with the human T-lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV). By December 1984, 2.4% of the men had the syndrome; mortality attributable to the syndrome in 1984 was 600/ 100 000. For each man with the syndrome in a representative sample of 474 cohort members seen in 1984, 7.5 men had generalized lymphadenopathy, 1.1 had other prodromal findings, and 0.8 had hematologic abnormalities. Prevalence of serum antibodies to HTLV-III/LAV, measured by an enzyme-linked immunosorbent assay, increased from 4.5% in 1978 to 67.4% in 1984. Of 31 persons who were seropositive and without the syndrome between 1978 and 1980, 2 developed the syndrome and 8 developed related conditions during a median follow-up of 61 months. Over a 6-year period, two thirds of cohort members were infected with HTLV-III/LAV and almost one third developed related conditions.