Reports on intrathecal administration of penicillin in treating infections of the central nervous system are becoming numerous. Recently intraventricular injection of penicillin has been employed when meningitis did not respond to parenteral or intrathecal modes of administration.1The direct application of penicillin to wounds of the cerebral cortex in the treatment of injury to the head has also been suggested.2Our interest in the effect of penicillin on the central nervous system was aroused by observing convulsive seizures following intraventricular injection of the drug in a case of ventriculitis.3Experiments were then planned to investigate the effect of the drug when administered intracisternally, intraventricularly and locally to the cerebral cortex either by application to the subdural space or by intracortical injection. Such experiments were performed, and it was observed that certain doses of penicillin so administered to mice, cats, dogs and monkeys gave rise to convulsive manifestations.