OBJECTIVE: The authors sought to determine whether rates of depressive symptoms change from early- to late-stage HIV-1 infection and to determine the predictors of depressive symptoms as AIDS develops. METHOD: The data for this study were from 911 HIV-seropositive men- community volunteers from four U.S. cities-who entered the 10-year Multicenter AIDS Cohort Study without a diagnosis of AIDS and subsequently developed AIDS. The subjects underwent semiannual follow- ups during the study period. The outcome measures-overall depressive symptoms, nonsomatic depressive symptoms, syndromal depression, and severe depression-were assessed over the 5 years before and the 2 years after AIDS diagnosis from responses on the Center for Epidemiologic Studies Depression Scale (CES-D Scale). RESULTS: Depressive symptoms were stable over time from month 60 to month 18 before AIDS developed. However, beginning 12-18 months before AIDS diagnosis, there was a significant rise in all measures of depression, which reached a plateau within 6 months before AIDS developed. At this plateau, there was a 45% increase in mean CES-D Scale scores above baseline. An elevated CES-D Scale score in the earlier stages of infection, a self-report of AIDS- related symptoms (such as rash and lymphadenopathy), concurrent unemployment, cigarette smoking, and limited social supports were consistent predictors of higher rates of depression as AIDS developed. CONCLUSIONS: There is a dramatic, sustained rise in depressive symptoms as AIDS develops, beginning as early as 18 months before clinical AIDS is diagnosed. Prior depression, HIV-disease-related factors, and psychological stressors contribute to this rise. This robust phenomenon invites further characterization.