Valproic acid is a useful antiepileptic drug, with occasional gastrointestinal side effects. Hepatotoxicity is the most serious adverse reaction and, although rare, it can be fatal. Risk factors for hepatotoxicity are an age of less than two years, polytherapy and mental retardation; it has been rarely reported in adults. We report three mentally retarded adult patients receiving polytherapy, who developed valproic acid induced hepatotoxicity. Two patients had a symptomatic hepatitis with a concomitant paradoxical increase in seizure frequency and one an asymptomatic alteration of hepatic function tests. After discontinuing the drug, the hepatitis subsided. We conclude that hepatotoxicity must be considered as a possible side effect of valproic acid and we suggest some recommendations for its early detection.