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We report a case of pancreatitis with fatal liver failure, in a 21-year-old, mentally retarded patient, taking valproic acid (VPA) therapy, together with a review of the literature of this rare side effect. Until March 1991, only 24 cases of isolated pancreatitis and six cases (including ours) of pancreatitis with hepatic failure under VPA treatment have been published. Most of the patients were less than 20 years old, and injury to the pancreas developed during the first year of therapy in 72% of the patients, approaching a mortality of 21%. Pancreatitis associated with liver failure has a poor prognosis mainly because of the VPA hepatotoxicity. It seems that the pancreatic side effects fluctuate between two extremes: asymptomatic hyperamylasemia and fatal pancreatitis.