The hemodynamic and renal effects of atriopeptin II were investigated in rats, using electromagnetic flowmeters and thermodilution and clearance techniques, and its direct cardiac effects were studied in isolated rat atria and ventricular muscle strips. Atriopeptin II had no effect on the rate or force of contraction of rat cardiac tissue in vitro. In anesthetized rats, i.v. injections of 1, 3, 5, and 7 micrograms/kg induced only transient hemodynamic effects: blood pressure (BP) was briefly reduced, and renal blood flow (RBF) but not mesenteric blood flow (MBF) increased. Infusions over 30 min at rates of 0.3, 1, 3, and 10 micrograms/kg/min caused a fall in BP, mediated by a reduction of cardiac output (CO); RBF and MBF were decreased in a dose-related manner, and systemic and regional vascular resistances rose. A reduction of RBF was also observed in clearance experiments, but glomerular filtration rate remained unchanged and the filtration fraction increased significantly. Natriuresis occurred at all rates of atriopeptin tested (0.3, 1, and 3 micrograms/kg/min i.v.) These results suggest that i.v. injection of atriopeptin II induces transient hypotensive and regional vasodilatory effects. Upon i.v. infusion, BP is lowered by way of a reduction in CO, which is accompanied by systemic and regional vasoconstriction. The decrease in CO cannot be ascribed to a direct cardiodepressant action, and the effects on regional blood flows are probably due to reflex activation. The natriuretic effects of atriopeptin II are independent of renal vasodilatation and may be attributable to changes in intrarenal hemodynamics or to direct tubular effects.