Serial plasma samples collected after an acute administration of valproic acid, (VPA, 15 mg/kg as oral solution) in epileptic patients were selected for this study. The plasma samples were selected from three different groups of patients; patients on phenobarbital and phenytoin with clinical VPA intolerance (group A); patients on phenobarbital and phenytoin without clinical VPA toxicity (group B); and patients without phenobarbital and phenytoin and without clinical VPA toxicity (group C). Plasma samples from 6 patients per group were analyzed for carnitines and ammonia. Ammonia levels during acute study increased significantly (P less than 0.05) in patients who experienced VPA intolerance, while no changes were found in the other patients. After acute VPA administration, total carnitine was unchanged but free carnitine was decreased (P less than 0.05) and carnitine esters were increased (P less than 0.05) in all groups of patients studied. No difference in carnitine profiles was seen between patients with or without evidence of VPA administration has an important effect on carnitine metabolism. However, unlike the acute effect on ammonia metabolism, this acute effect does not seem to be correlated with any associated antiepileptic therapy, nor does it predict clinical VPA intolerance.