We describe a 75-year-old patient who presented with severe cholestatic liver disease. He had been receiving methyldopa, 250 mg daily, for 6 years. An extensive evaluation failed to reveal extrahepatic obstruction or serologic evidence of viral hepatitis. A liver biopsy disclosed marked cholestasis, without hepatitis, and was compatible with a rare form of methyldopa-induced liver injury. Cessation of drug treatment was followed by a slow but complete recovery. Cholestasis is a rare manifestation of methyldopa hepatotoxicity. Although methyldopa-associated liver injury usually appears after about 4 weeks of treatment, a history of a much longer exposure does not exclude this entity.