Plasma ACTH and corticosterone were measured under basal conditions and after ether or tourniquet stress during the nadir (a.m.) and zenith (p.m.) of the nycterohemeral pituitary-adrenal cycle. Exogenous ACTH was also given at these 2 times to assess adrenal sensitivity to ACTH and the maximal adrenal capacity for corticosterone secretion. Ether stress caused a greater rise in plasma ACTH in the a.m. than in the p.m., even though basal plasma ACTH and corticosterone concentrations were lower in the a.m. than in the p.m. When given in the p.m., pentobarbital anesthesia depressed plasma corticosterone and ACTH to the a.m. level; under these conditions the rise in plasma ACTH produced by tourniquet stress was the same in the a.m. and p.m. Both tourniquet and ether stresses caused maximal activation of adrenal corticosterone secretion, but ether produced a much greater rise in plasma ACTH. It is concluded that: (1) the greater ether-induced rise in plasma ACTH in the a.m. than in the p.m. is probably due to the lower plasma (and probably tissue) corticosterone concentration at that time; (2) the plasma ACTH concentration for inducing maximal adrenal activation is relatively low; and (3) the higher basal levels of plasma corticosterone in the p.m. than in the a.m. are due to a slight increase in basal ACTH secretion in the p.m.