OBJECTIVE To determine changes in causes of death, survival, and organ system distribution of major opportunistic infections and neoplasms in adults dying with the acquired immunodeficiency syndrome (AIDS) following the widespread use of antiretroviral therapy and prophylaxis for opportunistic infections since 1988. METHODS A retrospective review of autopsy records with gross and microscopic pathologic findings, laboratory data, and clinical histories in cases of AIDS, comparing findings from 1982 through 1988 with those from 1989 through May 1993. METHODS All autopsies were performed on persons dying in the metropolitan Los Angeles, Calif, area from January 1982 through May 1993. RESULTS In 565 adult cases of AIDS at autopsy, Pneumocystis carinii pneumonia (PCP) remained the most common cause of death, but both the frequency of and number of deaths of PCP declined over time. Deaths from bacterial sepsis, cytomegalovirus infection, Mycobacterium avium complex infection, and toxoplasmosis also declined during this period, but mortality from fungal infections, tuberculosis, encephalopathy, and causes unrelated to AIDS increased. The death rate from malignant lymphoma remained high. Kaposi's sarcoma (KS) continued to occur more frequently in patients whose risk factor for human immunodeficiency virus infection (HIV) was homosexuality or bisexuality, but the death rate from KS was greatest for patients with a risk factor of blood exposure to HIV. Survival was shorter and deaths from tuberculosis more common in patients with a history of intravenous drug use. Overall survival of patients in other AIDS risk groups increased over time, particularly in those treated with antiretroviral therapy. The organ system distribution of major opportunistic infections and neoplasms was similar throughout the years of the study. The lung was the most frequent organ involved by AIDS-associated diseases leading to death, followed by the gastrointestinal tract and the central nervous system. CONCLUSIONS The causes of death in AIDS have evolved since 1988 following the widespread use of prophylactic and antiretroviral therapies in patients with HIV infection. This has occurred primarily from changes in overall frequency and death rates from infections. Organ system involvement by AIDS-associated diseases has not changed significantly over time.