The effect of acute systemic hypotension on the heart was studied in the dog by maintaining coronary artery pressure at a constant level, using a separate perfusion system while the other tissues were perfused by a second separate extracorporeal circuit. In 14 dogs the systemic arterial pressure was acutely lowered to 25 mm Hg by a reduction in arterial flow. Dogs with total cardiac denervation showed no change in heart rate, myocardial contractile force, left atrial, or pulmonary arterial pressures during a 12-min period of hypotension. Normal dogs demonstrated an initial increase in heart rate of 9%; this was followed in 5–6 min by a 31% decrease in heart rate. Heart rate returned to control levels when systemic pressure was elevated or if the vagus nerves were divided. Dogs treated with reserpine showed only the decrease in heart rate and no initial cardiac acceleration. This study shows that the slowing of the heart observed during acute hemorrhage results, at least in part, from increased vagal activity.