In this study, the influence of nitric oxide (NO) and adenosine systems on penicillin-induced epileptiform activity was examined in rats. NO donor, sodium nitroprusside (SNP, 50 mu g/rat, i.c.v.) reduced the frequency but not the amplitude of epileptiform discharges. Non-selective NOS inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 100 mu g/rat, i.c.v.) practically did not exert any effect on the spike frequency and amplitude. Adenosine (100 mu g/rat, i.c.) reduced spike frequency but not the amplitude, whereas theophylline (100 mu g/rat, i.c.v.) increased the mean spike frequency and amplitude of penicillin-induced epileptiform discharges. Co-injection of theophylline and L-NAME did not cause a further increase in the epileptiform activity compared with theophylline. When NO production was blocked with L-NAME, the inhibitory effects of adenosine were lost. The obtained results suggest that NO and adenosine may decrease penicillin-induced epileptiform activity in rats and that NO, at least in part, may mediate the anticonvulsant effect of adenosine.