OBJECTIVE Patients infected with the human immunodeficiency virus (HIV) have been described to have an unusual form of renal disease known as HIV-associated nephropathy. This condition is characterized by severe proteinuria, rapid progression to renal insufficiency, and a morphologic pattern of focal segmental glomerulosclerosis (FSGS) on renal biopsy. Despite increasing awareness of this entity, the epidemiology and clinical course of HIV-associated nephropathy are not yet well defined. We therefore decided to study HIV-infected patients with this biopsy-proven pattern of focal sclerosis. METHODS Using life-table analysis, we evaluated the clinical features and course of 26 patients with HIV infection and biopsy-proven FSGS and compared them with those in 24 subjects with HIV infection who had no glomerular disease at autopsy. RESULTS The group with FSGS had a higher percentage of blacks (96% versus 46%) and intravenous drug abusers (42% versus 17%), and had a higher mean serum creatinine level (5.4 mg/dL versus 1.0 mg/dL) than the group of HIV-infected subjects without glomerular disease. At the time of diagnosis of FSGS, six patients had clinical acquired immunodeficiency syndrome (AIDS), eight had AIDS-related complex (ARC), and 12 patients had no evidence of AIDS or ARC. The progression to end-stage renal disease for all patients was rapid, with a median time to dialysis of 10.9 weeks. Duration of patient survival was dependent upon the stage of HIV infection at the time of diagnosis of renal disease. Patients who presented with AIDS had a median survival of 1.9 months, compared to a median survival of 3.6 months for those with ARC and 9.7 months for initially asymptomatic HIV carriers (p less than 0.05). Fifteen patients either presented with or developed AIDS during the course of the study, and all died as a consequence of their immunodeficiency. Survival curves from the diagnosis of AIDS to death were similar in the group with HIV-associated nephropathy (7.3 weeks) compared to the control AIDS group without renal disease (6.9 weeks). CONCLUSIONS Our data indicate that FSGS associated with HIV infection can occur before other manifestations of AIDS, is more common in blacks and in intravenous drug abusers, and is rapidly progressive to uremia. Patient survival is dependent upon the stage of HIV infection. These findings may prove useful in devising more effective strategies for the care of this growing patient population.