The effects of mazindol (1 mg or 10 mg/animal, p.o.) on local cerebral utilization of glucose were studied by the quantitative autoradiographic [14C]2-deoxyglucose method in conscious adult male rats. Significant increases in local cerebral utilization of glucose were observed 2 hr after administration of 10 mg of mazindol in 10 out of 37 anatomically discrete regions examined. These 10 areas included regions rich in dopaminergic receptors (substantia nigra, globus pallidus), and also regions with few dopaminergic receptors (cerebral cortex, thalamus, cerebellum). Only the habenular nucleus showed a significant decrease in utilization of glucose induced by the administration of 10 mg of mazindol. No significant changes in local cerebral utilization of glucose were observed following the administration of 1 mg of mazindol. The fact that the pattern of utilization of glucose observed in this study resembled that produced by apomorphine, a putative dopaminergic agonist, indicates that the pharmacological effects of mazindol are related to the dopaminergic system.