Systemic amyloidosis has recently emerged as a major cause of nephropathy among heroin abusers in New York City. Although focal glomerulosclerosis is typically seen in intravenous drug abusers who present with the nephrotic syndrome, those who escape this complication are at risk for the later development of amyloidosis related to their use of the subcutaneous route. Twenty such addicts identified between 1981 and 1984 are described. Patients typically present with chronic suppurative skin infections, edema, the nephrotic syndrome, benign urinary sediment, and normal-sized or enlarged kidneys. Tubular dysfunction, particularly renal tubular acidosis and diabetes insipidus, is frequent. Progression of renal insufficiency is characteristically rapid. Prolonged survival of heroin abusers and exhaustion of intravenous access requiring recourse to the subcutaneous route underlie the occurrence of amyloidosis in the addict population. Chronic suppurative skin infection consequent to repeated subcutaneous injection appears to be the underlying cause.