The effect of different alpha 2-adrenoreceptor subtype agonists and antagonists on adrenocorticotrop hormone (ACTH) and beta-endorphin release induced by ether stress was examined. Ether inhalation-induced ACTH and beta-endorphin increase was inhibited by i.c.v. administration of 30 micrograms but not 1 and 10 micrograms clonidine (alpha 2-adrenoreceptor agonist). I.c.v. oxymetazoline (alpha 2A-adrenoreceptor agonist; 1-10-30 micrograms) or the alpha 1-agonist methoxamine (100 micrograms/rat) failed to inhibit the stress-induced rise. Pretreatment with the alpha 1/alpha 2B.C-antagonist prazosin (0.5 mg/kg, i.p.) prevented the effect of clonidine on the ether stress, while the alpha 1/alpha 2A-antagonist WB-4101 (0.5 mg/kg, i.p.) was unable to counteract the inhibitory effect of clonidine. Prazosin alone had no effect on the ether-induced plasma ACTH and beta-endorphin elevation. These results suggest that noradrenaline in the central nervous system may inhibit the stress-induced hypothalamo-pituitary-axis and pituitary beta-endorphin activation via alpha 2B.C-adrenoceptor subtypes and prazosin may antagonize its effect on these receptors.