Acquired immunodeficiency syndrome (AIDS) surveillance data for both the United States and San Francisco indicate that Kaposi's sarcoma is more common in homosexual and bisexual men with AIDS than in other adults with AIDS, and that the proportion of newly diagnosed AIDS cases presenting with Kaposi's sarcoma has been significantly declining over time. The changing epidemiology of Kaposi's sarcoma was analyzed in a well-characterized cohort of homosexual and bisexual men; laboratory and interview data from a sample of these men were evaluated for determinants of and cofactors associated with Kaposi's sarcoma. Among 1,341 men with AIDS, the proportion presenting with Kaposi's sarcoma declined from 79% in 1981 to 25% in 1989. Compared with other men with AIDS, men with Kaposi's sarcoma had a shorter interval from human immunodeficiency virus (HIV) seroconversion to AIDS diagnosis (median, 77 vs. 86 months). Men with and without Kaposi's sarcoma did not significantly differ with respect to number of sexual partners, history of certain sexually transmitted or enteric diseases, use of certain recreational drugs (including nitrite inhalants), or participation in certain specific sexual practices. The decline in Kaposi's sarcoma may at least partly be due to a shorter latency period from infection to disease. Although cofactors for the development of Kaposi's sarcoma may exist, many previously hypothesized agents were not supported by this analysis.