Influence of the ketogenic diet on plasma concentrations of antiepileptic drugs was investigated in an open clinical study of 51 children (mean age 6.6 years) with medically refractory epilepsy. The plasma levels of concomitantly used antiepileptic drugs were determined immediately before and 3 months after initiating the ketogenic diet. To compensate for adjustments in dosing, the plasma concentration in relation to the dose per kilogram of body weight per day, i.e. the level-to-dose ratio, was used for comparison; it was calculated as the plasma concentration (micromol/L) divided by the corresponding weight-normalized dose (mg/kg body weight/day) for each drug and child. The level-to-dose ratios of each drug before and during the diet were compared. No significant changes in these ratios could be found for valproic acid, lamotrigine, topiramate, clonazepam, or phenobarbital. In 16 children, the ratio of the free unbound concentration of valproic acid to its total plasma concentration was compared before and during the diet, but it did not change significantly. Thus, the ketogenic diet did not change the plasma concentrations of commonly used antiepileptic drugs in children in any significant way. Therefore, when initiating the diet, it does not seem necessary to adjust drug doses due to pharmacokinetic interactions.