THIS study was undertaken to evaluate the effect of ethanol intake on the anticonvulsive effects of Zonisamide (ZNS), a sulfonamide derivative. EL mice, a strain highly susceptible to seizures, were given a 10% ethanol solutionad libfor 1–4 weeks. Seizures in mice treated with ethanol for 1–3 weeks were decreased by ZNS at a dose of 75 mg kg−1, i.p., but those in mice treated with ethanol for 4 weeks were not suppressed. Serum ZNS concentrations following ethanol consumption for 1–4 weeks were higher than in untreated mice; however, brain ZNS concentrations following ethanol consumption were lower than those in untreated mice. These results suggest that alcohol intake decreases the brain concentration, but not the serum concentration.