Zonisamide (1,2-benzisoxazole-3-methane sulfonamide) is a new antiepileptic drug developed in Japan. This compound was proven to possess a strong inhibitory effect on convulsions of cortical origin, whether induced by electric or chemical stimuli, Regional distribution of C-14-zonisamide was investigated in rat brain using autoradiography. A high uptake of C-14 activity was observed in the cerebral cortex and the midbrain. A pair-match analysis of primary motor cortex versus primary sensory cortex revealed a slightly higher uptake in primary motor cortex. In the cerebellum, a higher uptake was observed in the cortex than medulla. Sagittal section analyses revealed that a high uptake of C-14 activity was observed in the cerebral cortex and colliculus, and a moderate uptake was seen in the cerebellum, thalamus, hypothalamus, and striatal body, thus suggesting the distribution of C-14-zonisamide is similar to that of flunitrazepam and phenytoin.