Of the 92 patients with the acquired immunodeficiency syndrome (AIDS) who were seen at our institution over a two-year period, 9 acquired the nephrotic syndrome (urinary protein greater than 3.5 g per 24 hours) and 2 had azotemia with lesser amounts of urinary protein. Five of these 11 patients had a history of intravenous-heroin addiction, but in the remaining six, there were no known predisposing factors for nephropathy. In nine patients (including the six non-addicts) the course of renal disease was marked by rapid progression to severe uremia. Renal tissue examined by biopsy in seven patients and at autopsy in three revealed focal and segmental glomerulosclerosis with intraglomerular deposition of IgM and C3. In the 11th patient, renal biopsy revealed an increase in mesangial matrix and cells, with deposition of IgG and C3 consistent with a mild immune-complex glomerulonephritis, and severe interstitial nephritis. We conclude that focal and segmental glomerulosclerosis may be associated with AIDS and suggest that rapid deterioration to uremia may characterize this renal disease.