1. In rats and in at least some other species, IV and IVT AII stimulate ACTH secretion. 2. Although AII increases ACTH secretion by a direct action on pituitary cells in vitro, it appears to act instead by stimulating CRH secretion in vivo. 3. The CRH stimulating effect of circulating AII is mediated by an action of the AII on one or more of the circumventricular organs of the brain. 4. AII administered into the cerebral ventricles and, presumably, centrally generated AII, increase CRH secretion by acting on AII receptors inside the blood-brain barrier as well as in the circumventricular organs. 5. A possible role for the renin-angiotensin system in mediating the increase in ACTH secretion produced by stress has been suggested, and the degree of involvement may vary from one stress to another. However, as yet we have been unable to obtain any evidence that either circulating AII or centrally generated AII plays a role in the increase in ACTH secretion produced by ether stress in rats and surgical stress in dogs.