The effects of lesions of the dopamine (DA) nerve terminals in the medial prefrontal cortex (MPFC) on local cerebral blood flow (LCBF) and DA receptor binding in rats were investigated. 4 micrograms of 6-hydroxydopamine (6-OHDA) was infused stereotaxically into the area of the bilateral MPFC of rats pretreated with desmethylimipramine, and control rats received a vehicle solution. Twenty-four days after the operation LCBFs of 23 brain regions were measured using the quantitative autoradiographic N-isopropyl-p-[125I]iodoamphetamine technique D1 and D2 DA receptor binding in various brain regions was also quantified autoradiographically using [3H]SCH 23390 and [3H]YM 09151-2 as the respective ligands. 6-OHDA lesions of MPFC produced significant increases in LCBF of the nucleus accumbens, the dorsolateral portion of the caudate-putamen and the anterior cingulate cortex. The lesioned animals did not show decreased LCBF in MPFC per se. D1 and D2 DA receptor binding was not affected in any brain region examined. These results suggest that lesions of the DA nerve terminals in MPFC induce an enhancement of functional activity in the terminal regions of the subcortical DA systems, and that hypofunction of the mesocortical dopamine system does not elicit reduced metabolic activity in the prefrontal cortex.