The effect of applied positive airway pressure or PEEP on pericardial pressure was examined in closed-chest, anesthetized dogs with normal lungs and in animals with oleic acid-induced lung injury. Both groups were studied before and after vascular volume loading by dextran infusion. Pericardial pressure was measured using an air-filled flat balloon placed along the lateral left ventricular free wall within the pericardial space. A linear relation between right atrial pressure (RAP) and pericardial pressure (PP) was found (RAP = 3.9 + 0.78 PP, r = 0.76, p less than 0.01) that was independent of acute lung injury but was influenced by the application of PEEP. In the baseline volume condition, pericardial pressure increased linearly with an increase in PEEP to 15 cm H2O. After volume loading, pericardial pressure increased fourfold, but, surprisingly, did not change with applied PEEP. These relations were similar in the two groups despite a reduction in total respiratory system compliance in the oleic acid group. This suggests that transmission of airway pressure to the pericardial surface is independent of the presence of acute lung injury and that changes in pericardial pressure in response to PEEP reflect both the transmission of airway pressure to the pericardial surface and, presumably, PEEP-related changes in cardiac volume and ventricular compliance.