The effect of Nω-nitro L-arginine methyl ester (L-NAME) on penicillin-induced epileptiform activity was investigated in anaesthetized Wistar rats. Approximately 39.1 ± 5.7 min after penicillin G (3 million U/kg, i.p.) administration, large amplitude intermittent sharp waves appeared in the electrocorticogram. L-NAME (60 mg/kg, i.p.) injection 30 min before penicillin G administration significantly reduced the latency of epileptiform activity (12.9 ± 3.2). In other groups, when the epileptiform activity reached maximum levels, administration of L-NAME (300 μg/2 μl, i.c.v.) significantly increased the frequency of epileptic spikes, while saline and D-NAME (Nω-nitro D-arginine methyl ester, 300 μg, i.c.v.) were completely ineffective. These results suggest that L-NAME has proconvulsant effects and NO may be an endogenous anticonvulsant substance.