The major mechanism whereby positive end-expiratory pressure (PEEP) decreases cardiac output is believed to be a decrease in the pressure gradient for venous return. However, although PEEP increases right atrial pressure (PRA), It may also elevate mean systemic pressure (PMS), the static circulatory filling pressure that is the upstream pressure for venous return. In an intact canine preparation, we studied the effects of 15 cm H2O PEEP on cardiac output, PRA, and PMS (the equilibrium PRA during ventricular fibrillation). To examine the role of neurovascular reflexes, PEEP was applied before and after either carotid sinus and vagal denervation (CSV) or total spinal anesthesia with arterial pressure restored by epinephrine infusion (SAE). To examine the effects of PEEP-induced elevations of abdominal pressure, the abdomen was bound or widely opened and the abdominal contents exteriorized. With reflexes intact, neither binding nor opening the abdomen altered the rise in PMS during PEEP. CSV attenuated the rise in Pms by 17% (Control, 4.89 +/- 0.3 SE; CSV, 4.04 +/- 0.22 mmHg; p less than 0.01), and SAE attenuated it by 49% (Control, 4.21 +/- 0.27; SAE, 2.14 +/- 0.31 mmHg; p less than 0.00005). After either CSV or SAE, the rise in Pms was not affected by binding. PEEP decreased (Pms-PRA) only when the abdomen was bound because of a greater rise in PRA, or during SAE because of a lesser rise in Pms. Under control conditions, PEEP increased Pms and PRA equally [(PRA-Pms) = 3.89 +/- 0.26 without PEEP versus 4.13 +/- 0.29 mm Hg with PEEP]. We conclude that PEEP increases Pms by both reflex and mechanical means independent of increased abdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)