We evaluated the effects of phenytoin, carbamazepine, phenobarbital, sodium valproate, and ethosuximide on penicillin-induced spike foci. Phenytoin, carbamazepine, and phenobarbital at blood levels within or slightly above the human therapeutic range in humans increased spike frequency, decreased spike duration, and abolished after discharges. Ethosuximide and sodium valproate had no statistically significant effect even at blood levels considered toxic in humans. The experimental spike focus and the method of analysis appear useful for: (1) detection of new potentially anticonvulsant drugs, (2) classifying new potentially anticonvulsant drugs according to the type of clinical seizure for which benefit is most likely, and (3) comparing different anticonvulsant drugs.