When positive end-expiratory pressure (PEEP) is added to intermittent positive pressure ventilation, cardiac output and stroke volume frequently fall despite unchanged or increased transmural left ventricular end-diastolic pressure. To determine whether a part of the fall in stroke volume with PEEP is explained by depressed left ventricular systolic function (increased end-systolic volume at a given end-systolic pressure on PEEP) the authors measured left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and the corresponding pressures in nine patients with acute hypoxemic respiratory failure. Measurements were made before and after 10 cm H2O PEEP was added to the ventilator. PEEP reduced mean stroke volume from 71 to 62 ml and this was explained entirely by a reduction in end-diastolic volume from 135 to 112 ml (P less than 0.005). Despite reduced EDV, pulmonary wedge pressure increased from 12 to 14 torr on PEEP, indicating reduced diastolic compliance or unstressed volume of the left ventricle in these patients similar to that reported in dogs. The authors conclude that PEEP reduces venous return and cardiac output without depressing left ventricular pumping function because end-systolic volume decreased from 64 to 49 ml on PEEP despite identical blood pressures (78 torr). They speculate that PEEP might improve ventricular performance by increasing intrathoracic pressure and left ventricular pressure relative to systemic blood pressure in extrathoracic vessels.