A previously healthy 59-year-old man received chlorpropamide 250 mg/day for adult-onset diabetes. Within 1 month of starting the drug, he developed cholestatic jaundice and pseudomembranous colitis. The colitis worsened during subsequent treatment with multiple antibiotics and sulfasalazine. Oral vancomycin produced a prompt and total remission. One similar case of chlorpropamide toxicity manifested by jaundice and colitis has been previously reported. It is possible that the sulfonamide moiety of the chlorpropamide was implicated in the development of the colitis.