In situ hybridization histochemistry was used to investigate the putative regulation of cholecystokinin messenger RNA expression by dopamine in the rat striatum. Using this method, cholecystokinin messenger RNA was undetectable in the normal rat striatum. Dopamine depletion caused by a 6-hydroxydopamine injection in the medical forebrain bundle induced, two and four weeks after the injection, an increase of cholecystokinin messenger RNA expression in the ipsilateral striatum. The labeling was mostly restricted to the dorsolateral quadrant. At the cellular level, this corresponded to a slight but significant labeling of a moderate density of striatal neurons which most probably represent a subpopulation of medium-sized spiny neurons. Conversely, treatment with either haloperidol or SCH23390 for two weeks did not induce any detectable changes in cholecystokinin messenger RNA expression in the striatum while, as expected, an increase in the striatal enkephalin messenger RNA content was observed. These results suggest that the dopaminergic nigrostriatal pathway directly, or indirectly, regulates the expression of cholecystokinin messenger RNA in the striatum.