The role of α-adrenergic mechanism in the acute effects of morphine in the hypothalamo-pituitary-adrenocortical (HPA) and cardiovascular (CV) systems, and the interrelationship between the HPA and CV responses to α-adrenoceptor antagonists and/or morphine were studied by peripheral administration of prazosin, a selective αi-adrenoceptor antagonist, and yohimbine, a selective α<sub>1</sub>-adrenoceptor antagonist, in conscious, unstressed or ether-stressed rats. The test substances were administered intravenously or intraperitoneally in chronically cannulated or noncannulated rats. In the i.v. experiment, morphine (1 mg/100 g BW) rapidly induced a pronounced bradycardia and a short-lasting fall in blood pressure (BP), followed by a rise in BP, and increased plasma corticosterone concentration. Prazosin (0.5 mg/kg BW) induced a rapid fall in BP and tachycardia, and increased plasma corticosterone concentration. Pretreatment with prazosin did not block the effect of morphine on the CV system, but abolished the morphine-induced increment in plasma corticosterone concentration. Yohimbine (0.5 mg/kg BW) induced a rapid and a subsequent slowly developing rise in BP and tachycardia, and increased plasma corticosterone concentration. Pretreatment with yohimbine did not block the effect of morphine on the CV system nor alter the stimulatory effect of morphine on the secretion of corticosterone. In the intraperitoneal experiment, morphine (2 mg/100 g BW) stimulated the secretion of adrenocorticotropic hormone (ACTH) and corticosterone and prazosin (1 mg/kg BW) stimulated the secretion of corticosterone, but pretreatment with prazosin reduced the morphine-induced increment in plasma corticosterone concentration in unstressed rats. In stressed rats, morphine reduced the stress-induced increment in plasma ACTH and corticosterone concentrations and prazosin also reduced the stress-induced increment in plasma corticosterone concentration. Pretreatment with prazosin did not alter the inhibitory effect of morphine. Taken together with the established concept that morphine acts in the HPA axis primarily at the level of the hypothalamus, the results suggest that: (1) in unstressed rats, morphine acutely stimulates the secretion of corticotropin-releasing factor (CRF) and/or other ACTH secretagogues in the hypothalamus partly through noradrenergic and/or adrenergic pathways: morphine facilitates the secretion of these catecholamines which, in turn, release CRF via stimulation of central α<sub>1</sub>-adrenoceptors, rather than α<sub>2</sub>-adrenoceptors; (2) by contrast, in stressed rats, morphine inhibits the secretion of CRF and/or other ACTH secretagogues partly by attenuating central noradrenergic and/or adrenergic activity presumably via inhibition of release of these catecholamines acting on postsynaptic α<sub>1</sub>-adrenoceptors; (3) the stimulatory effect of morphine on the HPA system under unstressed conditions might be ascribable partly to the morphine-induced CV changes; (4) the morphine-induced initial CV depression is independent of α-adrenergic mechanisms.