We investigated gender-dependent differences of genistein (isoflavone phytoestrogen) treatment in a penicillin-induced experimental epilepsy rat model. Twenty-eight adult Wistar Albino rats (14 females and 14 males) were devided into four groups, control and genistein-treatmed males and females. Genistein (100 mu g/kg, i.p) or saline was given during 15 days before the electrocorticography (ECoG) recordings. The epileptiform activity was induced by penicillin G potassium salt (500 IU) injections into the left somatomotor cortex. Significant differences among the groups were found in the latency to onset of epileptiform activity. This value in the female control group was significantly longer than the latencies in the male control, male genistein, and female genistein groups (respectively, P = 0.002, 0.015, and 0.032). There were no significant differences regarding the spike/wave frequencies and amplitudes in epileptiform activity between female/male genistein and control groups within all observation intervals (P > 0.05). Thus, genistein exerts a proconvulsant effect in the penicillin-induced epilepsy model, and the effect demonstrates the clear gender specificity related to the specificity of hormonal backgrounds in males and females.