We studied effects on venous return of α-and β-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a β-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an α-adrenergic mechanism is responsible for a decrease in venous return.