BACKGROUND: Pioglitazone is an oral hypoglycemic agent in the thiazolidinedione class. Only one case of hepatotoxicity related to this agent has previously been reported. OBJECTIVE: To report the clinical course of a patient with hepatitis after therapy with pioglitazone. DESIGN: Case report. SETTING: A community hospital. PATIENT: A 49-year-old diabetic man taking pioglitazone, 30 mg/d. INTERVENTION: Discontinuation of pioglitazone therapy. MEASUREMENTS: Serum aminotransferase and bilirubin levels, standard blood tests for causes of hepatitis and cirrhosis other than drug toxicity, and liver biopsy. RESULTS: After 6 months of pioglitazone therapy, significant hepatic dysfunction developed. Blood tests excluded viral, metabolic, and autoimmune disorders. Liver biopsy showed mixed hepatocellular-cholestatic injury compatible with drug toxicity. After treatment with pioglitazone was discontinued, liver enzyme values returned to normal. CONCLUSION: Patients receiving pioglitazone may develop serious liver injury and should be observed for evidence of hepatitis.