We examined whether dopamine depletion in the medial prefrontal cortex of the rat differentially affects basal and evoked dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content in the subareas of the neostriatum and nucleus accumbens. Loss of approximately 80% of tissue dopamine content in the medial prefrontal cortex did not significantly alter basal tissue concentrations of dopamine or DOPAC or the DOPAC:dopamine ratio in either the nucleus accumbens core or shell or the medial or lateral neostriatum. However, tail pressure stress significantly increased the DOPAC:dopamine ratio in the nucleus accumbens shell of lesioned rats. Because dorsal and ventral areas of the medial prefrontal cortex preferentially innervate the core and shell, respectively, we sought to determine whether the selective effect of lesions on dopamine terminals in the shell of the nucleus accumbens are paralleled by greater dopamine loss in the ventral medial prefrontal cortex. 6-Hydroxydopamine decreased tissue concentrations of dopamine in both the dorsal (-74%) and ventral medial prefrontal cortex (-68%). In lesioned rats, few tyrosine hydroxylase-immunoreactive fibers remained in the dorsal medial prefrontal cortex whereas a dense innervation remained in the ventralmost area. The present data suggest that the influence of mesocortical dopamine neurons on the dopamine projection to the nucleus accumbens shell is expressed only under conditions of stress. Furthermore, lesion-induced alterations in dopamine neurons projecting to the nucleus accumbens shell are not due to a more extensive loss of dopamine terminals in the ventral than in the dorsal medial prefrontal cortex.