There are many factors, both intrinsic and extrinsic to the left ventricle, that can affect its function when negative intrathoracic pressure is imposed. In this study, we examined whether the left ventricular response to the afterload imposed by negative intrathoracic pressure was similar to that imposed by partial aortic constriction. We used steady-state right heart bypass to control pulmonary venous return to the left ventricle and reflex blockade to maintain constant heart rate and contractility. To impose negative intrathoracic pressure we used a pressure chamber fitted over a midsternal thoracotomy, which allowed steady negative pressure to be applied to all intrathoracic surfaces. Left ventricular volumes were measured from biplane cineradiograms of multiple 1-mm markers implanted in the left ventricular midwall. With cardiac output and heart rate constant, we compared the left ventricular response to two different levels of negative intrathoracic pressure and to increasing aortic pressure by partial aortic constriction. In each case, negative intrathoracic pressure produced a rise in the left ventricular end-systolic and end-diastolic volumes as well as transmural pressures similar to the effects of partial aortic occlusion. Thus, when cardiac output, heart rate, and contractility are maintained constant and all external restraints on the left ventricle are removed, the left ventricle responds in a similar manner to an increase in hydraulic load whether produced by a decrease in intrathoracic pressure or by partial aortic occlusion.