SynopsisThe purpose of this study is to determine the acute effect of morphine on ACTH secretion and to determine whether morphine has a direct action on the adrenal cortex by the adult female Wistar rat. ACTH was measured by the determination of corticosterone levels in adrenal glands, adrenal venous blood and circulatory blood. It should be emphasized that in this paper, mechanism of secretion of adrenal corticosterone by the acute effect (the early stage action) following morphine administration was described. Even in morphinization with five daily morphine (2mg/100g, B. W., i. p.) injections, the account of acute effect was determined immediately after the final injection of morphine administration. Morphine alone can not act as an inhibitor of ACTH release nor as an inhibitor of ACTH release due to histamine stress, and morphinization can not act to inhibit ACTH release or to block the effect of a histamine stress on the secretion of ACTH in the early stage action of the final morphine administration, as evidenced by corticosterone levels both in adrenal glands and in circulating blood of the intact rats. Morphine (2mg/100g,B. W., i. p.) alone caused stimulation of ACTH release as well as the final morphine injection of morphinization, and pretreatment of the rats with morphine(2mg/100g, B. W., i. p.) could not act to block the effect of a histamine (0.5 mg/ 100g, B. W., i. p.) stress on the release of ACTH in the early stage action of morphine administration. A detailed account of the effect of morphine or morphinization with four daily morphine injections on corticosterone levels both in adrenal and in adrenal venous blood of the hypophysectomized-ACTH-treated rat has been reported. Morphine (2mg/100g, B. W., i. p.) alone or with pretreatment of pentobarbital (1mg/100g, B. W., i.p.) does not directly interfere with the response of the adrenal cortex to exogenous ACTH in the early stage action of morphine administration. Morphinization with four daily morphine (2mg/100g, B. W., i. p.) injections in the early stage action following the directly act on adrenal corticoidogenesis in vivo. These results suggest in the early stage action of morphine administration that morphine acts to stimulate ACTH release at a higher level than the anterior pituitary and does not directly act on adrenal cortex, and that the acute effect of strong stimuli on the rate of ACTH release is not mediated by a decrease in the concentration of circulating adrenal corticosteroids.