The morphochemical and biochemical distribution of the adenylate cyclase-linked dopamine receptor, or D1 subpopulation, has been examined in the rat striatum following a chemical lesion of the dopaminergic nigrostriatal pathway. The cellular pattern of D1 dopaminergic binding was assessed using in vitro autoradiographic localization of [3H]SCH 23390 or [125I]SCH 23982, selective D1 receptor antagonists, 1 week following unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. The specific association of the D1 binding sites with cyclic AMP-immunoreactive striatal neurons was abolished after lesion of the dopaminergic nigral afferents. The morphochemical disruption of the caudate D1 dopamine binding sites in relation to cyclic AMP-positive elements, a large proportion of which are striatonigral neurons, probably contributes to the dysfunctions in this subpopulation of dopamine receptor after depletion of the catecholamine neurotransmitter.