The mechanisms of enhancement of cardiac output of unanesthetized dogs from 2.7 to 3.6 l min-1 during paced heart rate increase from 92 to 178 beats min-1 were studied in 92 trials with 5 dogs. This enhancement of cardiac output was accompanied by a 0.6 mm Hg fall in right atrial pressure and a 3.3 mm Hg fall in left ventricular end-diastolic pressure. The results are compatible with the hypothesis that an isolated rise in cardiac function shifts blood from the heart and lungs into the systemic circulation which increases the degree of filling of the peripheral vessels and hence increases mean systemic pressure. We postulate that decompression of both atria reflexly raises the tone of the peripheral vessels while the increase in arterial blood pressure reflexly lowers the tone. Apparently a balance is achieved that results in an elevated mean systemic pressure, displacement of the venous return curve to the right, and an increase in the amount of venous return that matches the enhanced cardiac output.