Stress stimulates secretion of the pro-opiomelanocortin (POMC)-derived peptides adrenocorticotropic hormone (ACTH), beta-endorphin (beta-END) and alpha-melanocyte-stimulating hormone (alpha-MSH) from the anterior lobe (AL) and intermediate lobe (IL) of the pituitary gland. The secretion of POMC-derived peptides from the AL and IL is differentially regulated and the relative contribution of the lobes may vary with the stimulus. We investigated (1) the relative importance of the AL and IL as source of POMC-derived peptides released in response to restraint and ether stress by selectively inhibiting the corticotropes of the AL by dexamethasone (DEX) or selectively inhibiting the melanotropes of the IL by bromocriptine (BR), and (2) whether beta-adrenergic blockade by propranolol could be used to discriminate between the stress-induced effect on POMC secretion from the AL and IL as has previously been suggested. Selective inhibition of AL secretion by DEX totally blocked the ACTH response to restraint and ether stress, but only partially inhibited the beta-END response. The alpha-MSH response to both stressors was not affected by DEX. Conversely, selective inhibition of IL secretion by BR totally blocked the alpha-MSH response to both stressors, partially inhibited the beta-END response but did not influence the ACTH response. In response to restraint stress, beta-END was secreted equally from the AL and IL, whereas the IL was the most important source of beta-END in response to ether stress. Blockade of beta-adrenergic receptors with propranolol inhibited the beta-END- and alpha-MSH responses to restraint stress whereas the ACTH response was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)