We investigated the role of the pericardium in the mechanism of shifts in the left ventricular (LV) diastolic pressure-volume relation produced by changes in circulating blood volume and by pericardial effusion. Twelve closed-chest anesthetized dogs were instrumented with pericardial and pleural balloons and intracardiac catheters for pressure measurements. We measured the volumes of the pericardium and the left and right ventricles by computed tomography (CT), integrating the area of CT cross-sections measured at 1-cm intervals from the cardiac apex to the aortic arch. The volumes of the pericardium and the cardiac chambers were changed by infusing 40 and 80 ml of dilute contrast medium into the pericardial space, by bleeding, and by rapidly infusing saline intravenously. Pericardial effusions of 80 ml reduced mean right ventricular volumes to 59% of control, whereas LV volumes were less severely compromised (81% of control). Total pericardial volume and pressure increased. Intravenous saline infusions, which raised right atrial pressure 10-15 mm Hg, produced increases of this magnitude in pericardial pressure. This was also the magnitude of the upward displacement in the LV diastolic pressure-volume relation after infusion. However, LV diastolic transmural pressure-volume coordinates fell along a single curve. Similar behavior was observed for the right ventricular diastolic pressure-volume relation. Pericardial transmural pressure-volume curves were described. When cardiac volume was altered by volume load and pericardial effusion, acute shifts in the LV diastolic pressure-volume relation were caused by changes in pericardial pressure, which, in turn, corresponded to changes in pericardial volume.