Epilepsy is a disorder characterized by recurrent seizures, which can increase the content of reactive oxygen in the brain. Active oxygen free radical scavengers such as ascorbic acid or alpha-tocopherol (vitamin E) might prevent epilepsy. A variety of animal seizure models exist which help to document the effects of vitamin E and specify its action. In this study, we have evaluated dose-dependent effect of alpha-tocopherol on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 100, 300, or 500 mg/kg of alpha-tocopherol was administrated intramuscularly (i.m.). alpha-Tocopherol (100, 300, or 500 mg/kg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. alpha-Tocopherol of 300, or 500 mg/kg significantly decreased the frequency of epileptiform activity in the penicillin-pretreated animals. The low dose of alpha-tocopherol (100 mg/kg) did not significantly change either amplitude or frequency of epileptiform activity. alpha-Tocopherol of 500 mg/kg i.m. was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The anti-convulsant effects of alpha-tocopherol appeared 80, 60, 30 min after alpha-tocopherol injection in 300, 500, and 3 day vitamin E supplemented groups. These data indicate that alpha-tocopherol decreases the frequency of penicillin-induced epileptic activity.