The specific binding of [ 3H]SCH23390 to D 1 and of [ 3H]raclopride to D 2 dopamine receptors was measured by autoradiography in the rostral and caudal halves of neostriatum and in the substantia nigra of adult rats subjected to near total destruction of nigrostriatal dopamine neurons by intraventricular 6-hydroxydopamine soon after birth. Three months after this lesion, [ 3H]SCH23390 binding (D 1 receptors) was slightly but significantly decreased in the rostral neostriatum (22%), but unchanged in its caudal half and in the substantia nigra. In contrast, [ 3H]raclopride binding (D 2 receptors) was considerably increased throughout the neostriatum (10–40%), while markedly decreased in the substantia nigra (80%). In the rostral neostriatum, there were no parallel changes in D 2 receptor messenger RNA levels, as measured by in situ hybridization on adjacent sections. Caudally, however, slight but significant increases in D 2 messenger RNA could be observed (10–20%). As assessed by quantitative iontophoresis, there was a marked enhancement (63%) of the inhibitory responsiveness of spontaneously firing units in the rostral neostriatum to dopamine and the D 1 agonist, SKF38393, in neonatally lesioned compared to control rats. On the other hand, responsiveness to PPHT, a potent D 2 agonist, appeared to be unchanged. Such opposite changes in the number of D 1 and D 2 binding sites, dissociated from the expression of D 2 receptor messenger RNA and from the sensitivity to dopamine and D 1 and D 2 agonists, suggested independent adaptations of these various parameters following the neonatal dopamine denervation of neostriatum. They also provided further evidence for mechanisms other than the dopamine innervation in the control of the expression of neostriatal D 2 receptor messenger RNA during ontogenesis, and emphasized that the effects of dopamine and its D 1 and D 2 agonists in neostriatum do not depend strictly on the number of D 1 and D 2 primary ligand recognition sites.