The adrenergic control of pituitary beta-endorphin release was investigated by testing the effect of various alpha and beta adrenergic drugs on the secretion beta-endorphin-like immuno-reactivity (beta-END-LI) from primary cell cultures of anterior and neurointermediate lobes as well as into plasma in vivo. Incubation of anterior lobe cells with several adrenergic agonists (10-7-10-5 M) evoked significant release of beta-END-LI with the following potency order; l-epinephrine greater than alpha-methylnorepinephrine greater than guanfacine = methoxamine = l-isoproterenol. The epinephrine- and isoproterenol-induced release from anterior lobes were both inhibited by phenoxybenzamine but not propranolol, suggesting mediation by alpha adrenoceptors. Release of beta-END-LI from cultured neurointermediate lobe cells was also stimulated 3-fold by epinephrine or isoproterenol (10-100 nM) but appeared to do so via a beta adrenergic mechanism because propranolol blocked their effects. Administration of l-epinephrine (100 micrograms/kg s.c.) or l-isoproterenol (200 micrograms/kg s.c.) to rats evoked a 3- to 4-fold increase in plasma beta-END-LI, which peaked 30 min after injection and was dose-dependent up to 500 micrograms/kg, Pretreatment with phenoxybenzamine (5 mg/kg i.p.) 30 min before epinephrine (100 micrograms/kg s.c.) inhibited the drug-induced rise whereas propranolol (2 mg/Kg i.p.) blocked the increase in plasma beta-END-LI after isoproterenol (200 micrograms/kg, s.c.) These results demonstrate that alpha and beta adrenergic stimulation selectively release beta-END-LI from cultured anterior and neurointermediate lobes, respectively. Furthermore, both mechanisms appear to be active in vivo.