Twelve dogs with poorly controlled idiopathic epilepsy were entered into a prospective, open-label, noncomparative study. Oral zonisamide was administered as an additional therapy at a dosage adequate to achieve serum drug concentrations of 10 to 40 microg/mL. Seizure frequency before and after initiation of zonisamide therapy was recorded. A dosing interval of q 12 hours was sufficient to maintain serum zonisamide concentrations within the therapeutic range. The mean dosage of zonisamide required was 8.9 mg/kg q 12 hours. Seven (58%) dogs responded favorably, experiencing a mean reduction in seizures of 81.3%. Five dogs had an increase in seizure frequency. Mild side effects (e.g., transient sedation, ataxia, vomiting) occurred in six dogs.