Two cases of severe acute hepatitis in patients taking flutamide for metastatic prostatic carcinoma are reported. Jaundice and marked increase in aminotransferases occurred after 6-8 weeks of treatment. Continuation of flutamide administration was associated with the development of hepatic encephalopathy and a marked prolongation of prothrombin time. One of the patients died of acute liver failure and the other survived after prolonged hospitalization. Rechallenge was not performed because of the severity of the clinical picture. Liver histology showed extensive hepatic necrosis. These two cases strongly suggest that flutamide, in addition to its cholestatic side effects, can induce acute hepatitis potentially with a fulminant and lethal course. Journal of Hepatology.