1. The effect of streptozotocin (STZ), a nitric oxide (NO) donor, on kainic acid (KA)-induced neurotoxicity was examined in Sprague-Dawley rats. 2. The administration of KA (8 mg/kg, i.p.) produced significant neurotoxicity accompanied with increased immunoreactivity for Fos-related antigen in the rat hippocampus. 3. Pretreatment with STZ (15 mg/kg, i.m.) significantly blocked the neurotoxicity induced by KA. 4. Thus, the neuroprotective effect of STZ may, at least in part, reflect the role of NO in inhibiting seizures.