Two cases of clinically manifest liver failure in patients with metastatic prostatic cancer treated with the non-steroidal antiandrogen flutamide combined with a luteinizing hormone-releasing hormone analogue are described. One patient developed severe hepatic insufficiency with jaundice, ascites and hepatic coma. The condition reversed after discontinuation of flutamide. The other patient only became jaundiced with a biochemical cholestatic pattern. Previous reports of hepatic adverse reactions only include elevated transaminase levels without clinical manifestations. The morphological lesions in the liver biopsy and the clinical condition may be due to a reversible interaction with metabolic processes in the hepatocytes.