We studied eight open-chest dogs to determine whether there is regional variation in pericardial contact pressure (PCP). Flat, air-filled balloons were used to measure PCP simultaneously over the lateral walls of the right and left ventricles while cardiac volume was varied by dextran infusion. End-diastolic and mean PCP were significantly higher over the left than right ventricle at high (20.3 +/- 1.0 mmHg) and middle levels (13.7 +/- 0.9 mmHg) of left atrial pressure. At high left atrial pressures, the end-diastolic PCP over the lateral left ventricle was 9.1 +/- 2.4 mmHg compared with 4.3 +/- 2.3 mmHg over the lateral right ventricle (P less than 0.05). At middle levels of left atrial pressures, end-diastolic PCP was 6.2 +/- 3.5 mmHg over the left ventricle and 1.5 +/- 2.4 mmHg over the right ventricle (P less than 0.05). These variations in PCP persisted after severing the pericardial diaphragmatic attachments and after turning the dogs such that one or the other balloon was dependent. Regional distribution of PCP was studied by positioning a single balloon sequentially at multiple ventricular sites. PCP was consistently higher over the lateral wall of the left ventricle than either the anterior or posterior walls of the right or left ventricle. After aortic occlusion, end-diastolic PCP increased more over the left than right ventricle. In contrast, with pulmonary artery occlusion, end-diastolic PCP increased more over the right than left ventricle. Pericardial pressure varies regionally, and a single pericardial pressure may be an oversimplification when used to describe pericardial restraint on the cardiac volume.