Fourteen children (6 M, 8 F) suffering from refractory epilepsy received LTG as add-on therapy. LTG was administered twice daily at dosages increasing up to 2 mg/kg/day (for patients taking VPA) or to 10 mg/kg/day for patients taking AEDs that induce hepatic metabolism. The drug was withdrawn for side effects in 3 cases (rash: two cases, hirsutism: one), because of increased seizure frequency in 2 cases and because of unchanged seizure frequency in one. One patient died from acute respiratory failure, after repeated respiratory tract infections. A decrease in seizure frequency after one year of treatment with LTG was observed in 6 of the 7 patients who completed the study. The median total seizure frequency decreased from 10.7 +/- 7.3 to 3.8 +/- 4.6 seizures per day. At the end of the study, seizure frequency had decreased by more than 50% in 2 patients, by more than 75% in 2 patients, and 2 patients were seizure-free; in the remaining patient seizure frequency was unchanged. The best results were obtained with plasma LTG concentrations ranging from 0.5 to 5.4 micrograms/ml; no further improvement was observed at higher LTG concentrations.