The purpose of this study was to determine whether children with epilepsy undergoing valproate therapy and who are otherwise healthy have lower levels of serum and muscle carnitine. A total of 50 patients with epilepsy, 3 to 14 years of age, who were treated solely with valproate and free of abnormal neurologic findings or nutritional problems were selected. The control group consisted of 30 healthy children. The total carnitine levels in serum were 28.1 +/- 10.3 and 55.6 +/-7.3 microg/mL, and the free carnitine levels in serum were 16.5 +/-10.2 and 44.6 +/-7.3 microg/mL, the total carnitine levels in muscle were 12.1 +/- 1.8 and 45.3 +/- 5.9 micromol/g noncollagen protein and the free carnitine levels in muscle were 5.6 +/- 1.6 and 39.3 +/- 6.0 micromol/g noncollagen protein in the valproic acid-treated and control groups, respectively (P < .05). In conclusion, valproate monotherapy depletes both muscle and serum carnitine levels in otherwise healthy epileptic children.