The presence of pericardial adhesions at resternotomy not only increases the operation time but also increases the risk of serious damage to the heart, great vessels, and extracardiac grafts. The reported prevalence of damage is 2% to 6%. The fibrinolytic activity of pericardial tissue may be a crucial factor in determining the extent of adhesion formation following primary operation. Ten patients undergoing cardiac operations were studied to assess the plasminogen activating activity of homogenates of pericardial tissue samples. Samples were taken at three times during the operation and the plasminogen activating activity was measured by means of a standard fibrin plate technique. Tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and plasminogen activator inhibitor-2 were also measured by means of enzyme-linked immunosorbent assays. Compared with its initial levels (median 2.06 IU/cm2, range 1.28 to 6.48 IU/cm2), the plasminogen activating activity of pericardial biopsy tissue was significantly reduced at 75 minutes (median 0.64 IU/cm2, range 0.12 to 2.44 IU/cm2, p < 0.01) and at 135 minutes (median 1.45 IU/cm2, range 0.12 to 4.39 IU/cm2, p < 0.05). The major plasminogen activator present was tissue-type plasminogen activator. Compared with its initial levels (median 2.34 ng/ml, range 1.03 to 6.42 ng/ml), subsequent tissue-type plasminogen activator values were also significantly reduced at 75 minutes (median 0.83 ng/ml, range 0.75 to 5.13 ng/ml, p < 0.005) and at 135 minutes (median 1.24 ng/ml, range 0.75 to 6.67 ng/ml, p < 0.05). Low levels of urokinase-type plasminogen activator were found in 5 of 10 patients. However, neither plasminogen activator inhibitor-1 nor plasminogen activator inhibitor-2 was detected. Examination with a light microscope showed both increasing pericardial mesothelial damage and increasing features of acute inflammatory changes with time. This study shows that plasminogen activating activity is present in pericardial tissue and that tissue-type plasminogen activator is the major plasminogen activator. The observed inflammatory changes and concomitant damage to the pericardial mesothelium, and the significant reductions in pericardial tissue-type plasminogen activator and plasminogen activating activity seen during cardiac operations, may be important factors contributing to the early development of pericardial adhesions.