Adenosine has potent anticonvulsant effects on various models of experimental epilepsy. In the present study, we examined the effects of focal and intracerebroventricular (i.c.v.) adenosine on penicillin-induced epileptiform activity in Wistar rats. The effects of theophylline, a non-selective adenosine receptor antagonist, were also researched. The recordings of electrocorticogram (ECoG) were carried out by using a data acquisition system, under urethane anesthesia. Adenosine was given in doses of 1, 10 and 100 mu g/rat via focal and i.c.v. 30 min after penicillin administration. Theophylline was injected in doses of 1, 10 and 100 mu g/rat by i.c.v. too. Adenosine administration significantly decreased the spike frequency while theophylline increased. Focal adenosine is more effective than i.c.v. adenosine. 100 mu g adenosine is an effective dose that causes a decrease in epileptiform activity during experiments. We also demonstrated that 100 mu g theophylline significantly increased epileptiform activity. our findings suggest that focal adenosine is more effective than i.c.v. adenosine on epileptiform activity. (c) 2006 Elsevier B.V. All rights reserved.