A 57-year-old male with mild impairment of renal function secondary to diabetic glomerulosclerosis developed acute renal failure (creatinine 32.4 mg/dl) associated with a generalized desquamative skin rash and peripheral eosinophilia shortly after initiation of antihypertensive therapy with captopril. An acute interstitial nephritis was demonstrated on renal biopsy, and improvement was temporally related to initiation of therapy with prednisone. A review of the literature revealed 5 similar cases in whom acute deterioration of renal function occurred following initiation of captopril and in whom there were features of a hypersensitivity reaction, including skin rash, fever, eosinophilia, azotemia, eosinophiluria, and a Coombs-positive hemolytic anemia. Renal biopsy, where available, revealed an acute interstitial nephritis. Observations from these cases suggest that, of the angiotensin-converting enzyme inhibitors, this syndrome appears to be specific for captopril, begins within the 1st month of therapy, is not dose-dependent, and generally resolves on cessation of therapy. Steroids may hasten recovery, but sufficient data are not available to confirm their efficacy.