The results of a third retrospective study of the US experience since 1986 with fatal hepatotoxicity associated with valproic acid (VPA) are reported from the Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA. In 29 case fatalities, the most common presenting signs were drowsiness, jaundice, vomiting, hemorrhage, seizure exacerbation, anorexia, and edema. Risk factors included young age, especially below 2 years when the risk was 1:600, polytherapy, developmental delay, and coincident metabolic disorders, especially Alpers’ disease. 
COMMENT. The authors advise avoidance of VPA in patients who are at greatest risk of developing liver toxicity. Liver transplant had been received by 28% of the patients in this study.