Two patients with progressive myoclonus epilepsy of the Unverricht-Lundborg type and with intractable seizures in spite of standard anticonvulsant regimens were treated with zonisamide. After zonisamide therapy was initiated, both had a marked decrease in seizure frequency and significant improvement of functioning. Serum zonisamide concentrations were 43 and 27 micrograms/ml, respectively, with doses of 8.8 and 10.5 mg/kg/d. Both patients also continue to receive valproic acid and a benzodiazepine.