Chronic carbamazepine treatment for a period of 2 weeks caused a highly significant increase in brain adenosine receptors in the rat. The carbamazepine was administered in food pellets in a diet that achieved clinically relevant total plasma concentrations of carbamazepine and its active-10,11-epoxide metabolite. Of the several brain areas examined, the cerebral cortex and hippocampus exhibited the most robust increases in [3H]cyclohexyladenosine (CHA) binding. Increases of 35-40% were observed in these brain regions whereas an 8-10% increase was seen in the cerebellum. The carbamazepine induced increase in brain adenosine receptors in all these areas persisted unabated at 1 and 5 days as well as 2, 4, and 8 weeks following termination of carbamazepine treatment, suggesting a relatively permanent alteration of the adenosine receptor by this drug.