The potential involvement of the sympathoadrenal system in stress-induced secretion of peptides from the intermediate lobe of the pituitary gland and the activation of the pituitary-adrenal axis was studied. Male Wistar rats were subjected to control procedures, to sympathectomy by chronic administration (8 weeks) of guanethidine and/or to medullectomy by adrenal enucleation 9 weeks prior to exposure to forced immobilization stress for various periods of time. In intact or sham-operated rats, immobilization caused a prompt increase of circulating norepinephrine, epinephrine (EPI), corticosterone and of immunoreactive adrenocorticotropic hormone (ACTHi), α-melanocyte-stimulating hormone (α-MSHi) and β-endorphin (β-ENDi). Peak levels of pituitary hormones were found after 10 min of stress exposure, but fell to less than 30% of these levels after 2.5 h of immobilization. Adrenal medullectomy, which abolished the stress-induced release of EPI, reduced the acute increase of plasma α-MSHi and β-ENDi, but dit not influence the acute increase of plasma ACTHi during immobilization stress. Also in medullectomized plus sympathectomized rats, the initial stress response of circulating ACTHi was not different from that of controls. Adrenal medullectomy with or without additional sympathectomy caused a marked increase in plasma ACTHi concentrations after prolonged stress exposure. We conclude that: (1) catecholamines originating from the adrenalmedulla facilitate the stress-induced secretion of intermediate lobe peptides (α-MSHi, β-ENDi); (2) catecholamines from the sympathoadrenomedullary system do not contribute to the acute release of ACTH during immobilization stress; (3) the sympathoadrenomedullary system is involved in the secondary reduction of circulating ACTHi levels seen during prolonged