Hypothalamic dopamine (DA), acting at DA D2-receptors (D2-R) on pituitary target cells, mediates peptide release and biosynthesis of rat pituitary anterior lobe (AL) prolactin, and neurointermediate lobe (NIL) pro-opiomelanocortin (POMC). We were interested in determining if dopamine agonists and antagonists were capable of modifying D2-R gene expression in these pituitary cells. Utilizing the recently published sequence of the rat D2-R, we isolated a rat D2-R cDNA clone by polymerase chain reaction, and have synthesized RNA probes to quantitate levels of D2-R mRNA by solution hybridization/nuclease protection assay. We report here that 5-day administration of the DA antagonist haloperidol led to significant increases in both D2-R mRNA and POMC mRNA in the NIL; the DA agonist bromocriptine caused a significant decrease in NIL POMC mRNA with no parallel change in D2-R mRNA. In contrast, no significant changes in D2-R mRNA in AL were observed following treatment with either the DA agonist or antagonist. These data provide evidence for tissue-specific regulation of D2-R mRNA in response to dopaminergic manipulation.