The decrease in left ventricular (LV) stroke volume during positive end-expiratory pressure (PEEP) has been attributed to reduced LV filling and a decreased contractile state. To assess the relative importance of each mechanism, we examined the effects of zero, 5, 10, and 15 cm H2O PEEP on LV end-diastolic volume (EDV) and end-systolic volume (ESV), and on LV contractile performance using instantaneous pressure-volume loops recorded with micromanometer-tipped and volume conductance catheters in the LV. The LV contractile state was determined using the LV end-systolic pressure-volume relations, the LV dP/dtmax-EDV relation, and the LV stroke work-EDV relation. The importance of autonomic reflexes was assessed by repeating the sequence of PEEP after beta-adrenergic blockade using metoprolol, 10 mg administered intravenously. LV EDV decreased from a baseline of 37.8 +/- 3.7 ml (+/- SEM) to 35.0 +/- 3.8, 28.7 +/- 2.9, and 25.9 +/- 2.6 ml with 5, 10, and 15 cm H2O PEEP, respectively (p less than 0.05 for each comparison), which paralleled the decline in stroke volume. In contrast, LV ESV did not change significantly with PEEP. The slope and position of the LV end-systolic pressure-volume relation and the slopes of the LV dP/dtmax-EDV relation and the LV stroke work-EDV relation (p = NS) were not altered during PEEP before or after beta-adrenergic blockade, indicating no depression of systolic contractile function. We conclude that the decreased LV stroke volume that occurs with PEEP is due to impaired LV filling (i.e., reduced LV EDV) without a concomitant depression of myocardial contractility.