The present study was carried out to test the possible effects of caffeine in improving the memory deficits observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP)-lesioned rats, an animal model of early stage Parkinson's disease. Caffeine at the doses of 0.1-0.3 mg/kg (intraperitoneal) reversed the impairing effect of the administration of MPTP (1 micromol/side) into the substantia nigra, compact part, of rats on the avoidance scores in the training and test sessions of a two-way active avoidance task. This effect was not due to a motor or sensory alteration because the caffeine-induced learning and memory improvement was independent of the locomotor stimulant effect of the drug and there were no differences in the reaction time of the animals to a footshock (unconditioned stimulus) or a sound cue (conditioned stimulus) after caffeine treatment. These results suggest that the reported dopamine/adenosine-receptor interaction can be used to restore defective learning and memory processes in Parkinson's disease and indicate that caffeine and other adenosine receptor antagonists are drugs with the potential for treatment of the cognitive disabilities of Parkinson's disease.