Whether the material properties of the pericardial membrane are the key determinants of the in situ pericardial pressure-volume relation is not known. Although both the pressure-volume relation of the intact pericardium and the stress-strain relation of isolated pericardial samples are nonlinear, it is not clear how closely these phenomena are related. To directly examine this question we compared the pressure-volume, pressure-normalized volume, and stress-strain relations of pericardia from six dogs tested both in situ and in vitro. The curves generated under the two sets of conditions were different. The transition from the compliant to the noncompliant portion of the curve was more acute under in vitro conditions. Nonlinear regression analysis using a monoexponential function of the form Y = alpha (e beta chi-1) showed beta, the proportionality constant for the slope of the curve, to be larger for each form of analysis under in vitro testing conditions as follows: 0.002 +/- 0.009 vs. 0.078 +/- 0.029, P less than 0.002 for pressure-volume; 3.52 +/- 1.75 vs. 11.03 +/- 5.31, P less than 0.005 for pressure-normalized volume; and 19.6 +/- 6.6 vs. 62.3 +/- 18.8, P less than 0.001 for stress-strain. These differences in the pressure-volume relation of the intrapericardial space in situ and the isolated pericardium in vitro suggest that pericardial attachments present in situ may buffer the loading of the membrane itself. We conclude that the pressure-volume relation of the intrapericardial space is only partly determined by the properties of the isolated pericardium alone and is also influenced by other components of the intact pericardium.