Kaposi's sarcoma (KS), the most common cancer in patients with acquired immunodeficiency syndrome (AIDS), occurs predominantly in homosexual men. However, the percentage of homosexual AIDS patients with KS has declined during the past 6 years. This and other findings suggest that one or more cofactors associated with the homosexual lifestyle, rather than a special viral strain, probably influence the development of KS in patients infected with the human immunodeficiency virus (HIV). Possible reasons for the decline include changes in homosexual behaviors, leading to the practice of safer sexual techniques, and a decrease in use of nitrite inhalants. Identification of the KS-AIDS cofactor(s) could be invaluable to developing prevention and treatment strategies.