We evaluated recent trends in the incidence of AIDS-related malignancies using Cox proportional hazards analysis in 622 men with well-characterized dates of HIV seroconversion in the San Francisco City Clinic cohort. By the end of 1996, 182 men had been diagnosed with Kaposi's sarcoma (KS), and 45 men had been diagnosed with lymphoma. The incidence of KS dropped from 3.5 to 0 per 100 person-years between 1993 through 1995 and 1996 (p = .07), whereas lymphoma incidence remained stable between these periods (1.4-1.8, p = .2). Combination antiretroviral therapy increased from 13% to 23% in 1993 through 1995 to 49% in 1996 and 79% in 1997. The decline in KS cannot be explained by earlier declines in HIV incidence, and concurrent increases in antiretroviral therapy suggests that control of viral replication may lead to a direct or indirect effect on KS pathogenesis. Failure to see such a trend for AIDS-related lymphoma may reflect inadequate follow-up time after widespread use of therapy or a need to treat earlier in the course of HIV infection to prevent HIV-associated lymphomagenesis.