Plasma total, free, and acyl carnitine levels were determined in four groups of children: (1) those treated with valproic acid as monotherapy (n = 43), (2) those treated with valproic acid plus other antiepileptics as polytherapy (n = 91), (3) those treated with other antiepileptic drugs alone (n = 43), and (4) normal patients (n = 89). The mean free carnitine level was significantly lower in both the valproic acid monotherapy (29.9 mumol/L) and polytherapy (21.4 mumol/L) groups compared with normal subjects (36.8 mumol/L); it was also significantly lower than that in patients treated with other antiepileptic drugs (36.7 mumol/L). Comparison of valproic acid polytherapy and monotherapy yielded significantly lower free carnitine levels in the polytherapy group. The ratios of acyl to free carnitine for monotherapy (0.41) and polytherapy (0.45) were significantly higher than that in the normal group (0.25). This study indicates that a general decrease in the carnitine pool should be anticipated in patients taking valproic acid polytherapy and, to a lesser degree, monotherapy. Carnitine levels in the group taking other drugs did not differ from normal.