The present study was designed to test the hypothesis that vasoactive compounds produced in the ischemic part of the body below an occluded aorta are responsible for the hemodynamic changes observed during cross-clamping of the thoracic aorta. The experiments were performed on 32 rabbits anesthetized with halothane that underwent experiments with cross-circulation; the blood from the inferior caval veins of rabbits A was pumped into the inferior caval veins of rabbits B. Simultaneously, exactly the same amount of blood was pumped from the jugular vein of rabbits B into the jugular vein of rabbits A. The aorta and inferior vena cava were exposed and then simultaneously cross-clamped directly below the diaphragm. The cross-clamping of the aorta and inferior vena cava in rabbits A was associated with a 29% to 44% increase in mean arterial pressure in rabbits B. The experiments support the hypothesis and suggest that endogenously produced humoral factors are responsible for at least one third to one half of the arterial hypertension that usually develops during aortic cross-clamping.