Dopamine plays an important role in modulating synaptic transmission in the striatum and has great influence on the function of the basal ganglia. Degeneration of dopamine neurons in the substantia nigra (SN) is the major cause of many neurological disorders, and the reduction of dopamine innervation results in alterations of dopamine receptors in the striatum. It has been shown that the nigrostriatal dopamine system has functional and neurochemical asymmetry. To investigate the lateralization of dopamine receptors in the striatum after dopamine denervation, the present study used quantitative autoradiography to compare the changes in dopamine receptor binding in the left and right striatum in rats after unilateral dopamine depletion. In comparison to control levels, dopamine D1)-like receptor binding, labeled with [3H]-SCH23390, in the dorsal striatum was reduced 2 weeks after unilateral lesions of the SN with 6-hydroxydopamine. D1-like receptor binding was decreased in the ipsilateral striatum following unilateral lesions of either the left or right SN. The left and right striatum responded similarly to unilateral SN lesions, as there were no significant differences in the percent decrease in D1-like binding in the two striata. In contrast, D2-like receptor binding, labeled with [3H]-spiroperidol, was significantly increased in the dorsal striatum following an ipsilateral SN lesion. Furthermore, the up-regulation of D2-like receptors in the right striatum was significantly greater than that in the left striatum after an ipsilateral lesion. The asymmetrical up-regulation of striatal D2 receptors after extensive dopamine depletion might contribute to the lateralization of the nigrostriatal system observed in some pathological conditions.