In the present study, we investigated the distribution of voltage-gated Na(+) channels (VGSCs) in the normal and epileptic hippocampus of gerbils (a genetic epilepsy model) in order to confirm the relationship between VGSC and seizure activity in these animals. There was no difference of VGSC I immunoreactivity in the hippocampus between seizure-resistant (SR) and seizure sensitive (SS) gerbils. VGSC II immunoreactivity was rarely detected in the perikarya of principal neurons and interneurons in the SR gerbil hippocampus. However, in the SS gerbil hippocampus, VGSC II immunoreactivity was densely observed in the somata of interneurons located in the stratum radiatum and stratum lacunosum-moleculare. Double immunofluorescent study showed immunoreactivity for calretinin (approximately 80% in VGSC II-positive neurons) or calbindin D-28k (approximately 20% in VGSC II-positive neurons) in VGSC II-immunoreactive neurons. VGSC II-immunoreactive neurons did not show parvalbumin immunoreactivity. These findings suggest that seizure activity in SS gerbils may be related to the selective hyperactivation of interneurons in stratum lacunosum-moleculare via the up-regulation of VGSC II expression, which leads to the disinhibition of CA1 pyramidal cells.