The glutamate decarboxylase activity in the rat cerebellum, frontal cerebral cortex, hypothalamus, substantia nigra and nucleus caudatus, was measured after either acute or chronic administration of (+)-amphetamine (1.35 and 5.4 mg/kg, i.p.). It was found that following 45 days of treatment the highest dose of the drug induced a selective increase of glutamate decarboxylase activity in the substantia nigra. Also in addition to the known changes in body weight, behavior and food-intake, some of the rats (5 out of 80 rats) treated with the highest dose of (+)-amphetamine developed a self-mutilating behavior. These results suggest that after the repeated administration of a high dose of (+)-amphetamine the activity of the striatonigral GABAergic pathway is increased and supports the idea that gamma-aminobutyric acid output neurons might convey dopamine-related functions.