Prolonged valproic acid treatment results in secondary carnitine deficiency. In thirteen children paired samples of plasma were drawn at the onset of, and after 9 months of continuous valproic acid treatment. At onset free plasma carnitine values were age dependent; they increased during childhood (r = 0.59, p = 0.016). After 9 months: 1 - mean plasma free carnitine decreased by 40%, from 32.7 mumol/l to 20.9 (p 0.0008 and 3% overlap; 2 - plasma total carnitine decreased by 20%, from 34.9 mumol/l to 27.1 (p 0.016 and no overlap); and 3 - the esterified/free carnitine ratio increased by 40%, from 0.28 to 0.39 (p 0.011 and no overlap). In two out of thirteen patients clinical symptoms were observed, fatigue, besides the biochemical evidence of carnitine deficiency. In four others only biochemical deficiency was found. If the child complains of fatigue during prolonged valproic acid treatment, it is advised to supplement carnitine. A dose of 15 mg/kg body weight is effective to reverse the clinical symptoms of carnitine deficiency within a week. The dose to prevent deficiency is not yet established.