The intermediate lobe of the rat pituitary gland is a homogeneous population of cells which synthesize and secrete various peptides related to ACTH and lipotropin derived from a common precursor, proopiomelanocortin. Catecholamine beta-receptor (beta-adrenoceptor) and dopamine receptor which are present in the intact cells of the intermediate lobe, remain functional in the enzymatically dispersed cells. In this study we investigated the mechanism by which beta-endorphin is released from the dispersed cells of the neurointermediate lobe of the rat pituitary gland. 1-Isoproterenol stimulated the release of immunoreactive beta-endorphin-like peptide (IR-beta-Ep) and the accumulation of adenosine 3', 5'-monophosphate (cAMP). On the other hand, dopaminergic drugs, apomorphine, bromocriptine, dopamine, lergotrile and lisuride, decreased the rate of release of IR-beta-Ep. Dopamine also inhibited the stimulatory effects of 1-isoproterenol on the release of IR-beta-Ep and cAMP accumulation. Dopamine antagonists, fluphenazine and sulpiride, diminished the inhibitory effects of dopamine on the release of IR-beta-Ep and cAMP accumulation which were stimulated by 1-isoproterenol. it has been reported that cholera toxin enhanced the release of IR-beta-Ep and the accumulation of cAMP in the rat neurointermediate lobe. After preincubation in the incubation medium containing 30 nM cholera toxin for 2 hours, the cells (CT cells) showed spontaneous release of IR-beta-Ep and cAMP accumulation. 1-Isoproterenol had no effect on the release of IR-beta-Ep and cAMP accumulation in CT cells. Dopamine, however, inhibited both the release of IR-beta-Ep from CT cells and cAMP accumulation in CT cells. These results suggest that dopamine may be involved in the regulatory mechanism of IR-beta-Ep release from the dispersed cells of the rat neurointermediate lobe.