Twenty-one patients developed acute renal failure in association with nontraumatic rhabdomyolysis and myoglobinuria. The illness followed an overdose of ethanol, heroin, or other depressant drug in 18 patients. Lethargy or coma was present in 17 patients and muscle swelling in 11. Evidence of rhabdomyolysis included markedly elevated creatine phosphokinase, myoglobinuria, and aldolase in blood. Initial biochemical findings were similar to those of acute renal failure due to other causes, but the abnormalities were exaggerated. There was a disproportionate rise in serum creatinine concentration in relation to serum urea nitrogen concentration. Profound hyperuricemia was present in most patients. Transient hypercalcemia developed during the diuretic phase in 5 patients. One patient died. We conclude that nontraumatic myoglobinuria with acute renal failure is not infrequent and may occur after an overdose of ethanol or heroin. The disease has good prognosis despite severe hypercatbolism and untreated profound hyperuricemia.