To investigate the impact of changes in the level of the endogenous atrial natriuretic factor (ANF) on pituitary-adrenocortical activity, the secretion of corticotropin (ACTH) and corticosterone was studied under the conditions of enhanced and decreased circulating ANF levels in rats. Volume expansion (intravenous infusion of 5 ml of saline within 2 min) induced significant elevation in ANF levels 5 min after the infusion, whereas ACTH levels remained unchanged during the first 20 min and were elevated only at 40 min, i.e. at the time when ANF levels were again normal. Water deprivation for 48 h resulted in decreased ANF levels and increased corticosterone concentrations. ANF concentrations in peripheral blood obtained under thiopental anesthesia were lower than those in blood sampled in the same rats in conscious state. However, such changes were not observed in water deprived animals. In addition, ANF was found to be present in the hypophysial portal blood of anesthetized rats. In conscious sheep, portal ANF levels were significantly higher than those in peripheral blood. Our results support the suggestion of an inhibitory role of ANF in the control of ACTH release and indicate that this role of ANF is physiologically relevant.