Although angiotensin II (AII), a potent vasoconstrictor agent, has been reported to stimulate the hypothalamic-pituitary-adrenal (HPA) axis of laboratory animals, its role in the regulation of this axis in humans appears to be controversial. To examine this question, AII (Val5-AII amide) was infused intravenously into 19 male normal volunteers at the doses of 0, 1, 3.3 and 10 ng/kg/min for 30 min. AII had no effect on plasma ACTH, cortisol, corticotrophin-releasing hormone, arginine vasopressin, and atrial natriuretic factor concentrations, nor did it increase systolic or diastolic arterial blood pressure. On the other hand, AII caused a dose-dependent increase of plasma aldosterone concentrations, suggesting that the doses and the mode of AII infusion were effective. Thus, our data show that peripherally infused AII has no detectable effect on the HPA axis function in humans, at doses capable of stimulating plasma aldosterone secretion, its specific target hormone.