The purpose of this study was to determine in situ regional pericardial strains over a wide range of conditions. In five open-chest, anesthetized dogs we examined deformations from biplane cineradiographs of three sets of four 1-mm diameter steel beads glued to basal, midanterior, and apical regions of the pericardium during extremes of pericardial sac sizes (inferior vena caval occlusion, baseline, and tamponade). Finite deformation theory was used to determine the planar components of the Green's strains referenced to the completely unloaded, excised pericardium at the end of each experiment. From the Green's strains the principal components, E(I) and E(II), and the principal direction of strain were determined. The first strain invariant, I1 = E(I) + E(II), in the basal, anterior, and apical regions during caval occlusion (1.27, 0.73, and 0.67) did not differ significantly from those in the baseline state (1.43, 0.86, and 0.76) but increased significantly (P < 0.01) during tamponade to 1.54, 1.30, and 1.08, respectively. Using end systole during inferior vena cava occlusion as a reference, the directions of principal strain in each region during each condition were aligned parallel to the spine pointing toward the tail except at the base during tamponade when there was a 70-degrees rotation toward the left limb. The in situ dog pericardium is considerably strained by the underlying heart even during inferior vena cava occlusion, suggesting that a completely unloaded state cannot be achieved in situ. The regional differences in the direction but not the value of principal strain suggest that there are either regional variations in loading or material properties.