Heroin-associated nephropathy (HAN) occurs almost exclusively in black heroin abusers, suggesting a genetic link to the disease. To further study this possibility, the frequencies of HLA-A, B, C, and DR antigens were determined in a group of 47 black patients with HAN. Included in the analyses is a subgroup of 16 patients with biopsy-proven focal glomerulosclerosis. Patient frequencies were compared with three separate control populations, the first a normal black population from New York City, the second from a national registry, and the third a group of blacks with idiopathic focal glomerulosclerosis. Only the frequency of HLA-BW53 was consistently increased significantly in the patients as compared with the control groups. This finding supports the notion that a genetic predisposition may exist in the addicted population for the development of renal disease.