The pharmacology of a number of distinct dopamine (DA) systems was studied. Those DA projections possessing autoreceptors (striatum, olfactory tubercle and piriform cortex) exhibited large changes in DA metabolism in response to systemic administration of DA agonists and antagonists. In contrast, in those DA systems which lack autoreceptors (the prefrontal and cingulate cortical innervations) little or no response to DA agonists and a diminished response to DA antagonists was seen. When DA metabolism was inhibited by administration of a MAO inhibitor, reductions in HVA were observed in all brain regions studied. DA turnover appeared faster in the prefrontal and cingulate cortices than in the DA systems possessing autoreceptors.