Extracts from mammalian atrial tissue contain peptides referred to as atrial natriuretic factors(s) (ANF) that possess natriuretic, diuretic, and vasorelaxant properties. ANF circulates in the blood and the measured levels appears to be related to volume homeostasis. Our studies have shown that the decrease in mean arterial pressure produced by atriopeptin III (AP III) is due to a decrease in cardiac output secondary to a fall in stroke volume caused by lowered ventricular filling pressure. Preliminary data indicate that exogenous atriopeptin III enhances baroreceptor sensitivity as tested by phenylephrine infusion. Experiments designed to define the ANF and catecholamine responses to renal failure of differing severity and duration caused by reduction in renal mass demonstrated that renal failure when chronic (5 months) is associated with increased ANF and norepinephrine. Acute renal failure (4 weeks) induced by partial nephrectomy did not increase levels of ANF while an increase did occur at 48 hours following bilateral nephrectomy. Adrenergic activity was increased in both clinical situations.