PURPOSE: In order to determine the effect of neuronal nitric oxide synthase(nNOS) in seizure-related neuronal vulnerability of the hippocampus, the expression patterns of nNOS were examined in pentylenetetrazole(PTZ)-induced seizure groups and in PTZ seizure groups which were pretreated with nNOS inhibitors. METHODS: Male Sprague-Dawley rats weighing 200-300 g were used in PTZ(40 mg/kg)-induced seizure experiments. A specific inhibitor, 50 mg/kg 7-nitroindazole(7-NI), and a non-specific inhibitor, 50 mg/kg nitro-L-arginine(L-NA) were treated 30 min before the administration of PTZ to block nNOS. nNOS expression was evaluated by using immunohistochemical staining in the hippocampus of each group. RESULTS: The onset time of the first myoclonic jerk was markedly delayed in the 7-NI and the L- NA pretreated groups in comparison to the PTZ group. In addition, 7-NI markedly suppressed the severity of PTZ-induced seizures. The expression of nNOS in the hippocampal CA3 area was higher than that in CA1 area in the PTZ treated groups. In the L-NA pretreated groups, the expression levels in the CA3 and CA1 areas were lower than those of the PTZ treated groups. Interestingly, in the 7-NI pretreated groups, the nNOS expression levels in CA1 and CA3 areas were makedly lower than those of PTZ and L-NA pretreated groups. There was no expression in CA2 area of all groups. CONCLUSION: These results suggest that the hippocampal neurons expressing nNOS may be vulnerable to PTZ-induced seizures and that nNOS may play an important role in seizure-related neuronal vulnerability.