Peptides of cardiac origin, termed atrial natriuretic factors, possess both natriuretic and diuretic properties, actions which physiologically contradict those of the antidiuretic peptide, arginine vasopressin (AVP). In addition to their opposing actions in the kidney, the present results indicate that one of these factors, Atriopeptin III, can inhibit dehydration and hemorrhage-induced AVP release in the rat. 3 days of water deprivation resulted in elevated plasma AVP levels (36.1 ± 4.7 pg AVP/ml) which were significantly reduced following intravenous infusion of 0.02 (21.4 + 3.6), 0.2 (15.6 ± 1.6), and 2.0 (13.9 ± 3.8) nmol Atriopeptin III. Furthermore, 2.0 nmol Atriopeptin III significantly reduced post-hemorrhage levels (54.8 ± 13.7) of AVP to values that approximated resting levels (10.2 ± 3.7). The results suggest a role for cardiac peptides in the control of AVP release as well as the existence of a counterregulatory system, peptidergic in nature, for the maintenance of fluid and electrolyte homeost