Dopamine and norepinephrine levels were examined in 3 forebrain regions following unilateral lesions either in the ventral medial tegmental area (VMT) or in the substantia nigra. The dopamine and norepinephrine content of the nucleus accumbens, olfactory tubercle and corpus striatum were assayed ipsilaterally and contralaterally in unilaterally lesioned rats sacrificed 2, 5, 10, and 20 days after the placement of the lesions. In the nucleus accumbens and olfactory tubercle ipsilateral dopamine levels were significantly reduced below the contralateral levels at 2 days, and were decreased by 56% and 65%, respectively, 10 days after the lesion. A 30% reduction of dopamine levels occurred in corpus striatum as well, following lesions in the VMT. Lesions in the substantia nigra decreased ipsilateral dopamine levels by 68% in the corpus striatum, without affecting dopamine levels in the olfactory tubercle or nucleus accumbens. Norepinephrine levels on the side ipsilateral to the lesion did not significantly differ from contralateral levels in any of the 3 regions following lesions either in the VMT or in the substantia nigra. These results demonstrate the specificity of projection in the mesolimbic dopamine system as suggested by the original histofluorescence studies.