In an attempt to appreciate the changes that favour adhesion formation we compared the morphological and fibrinolytic changes that occur in human primary and reoperative pericardium. Ten patients undergoing primary elective open heart surgery and ten undergoing first time reoperative open heart surgery were studied. Pericardial samples were taken at four time points. At 0 (time A) and 30 (time B) minutes from the time of pericardiotomy (before the commencement of CPB), 30-50 minutes (time C) after the commencement of CPB, and then finally 10 minutes (time D) after the patient had been rewarmed. The fibrinolytic activity, as measured by the plasminogen activating activity (PAA), in the pericardial samples of the ten primary cases was compared with that in 5 of the reoperative cases. For the primary group, the PAA after 30 minutes of exposure (median 6.65 IU/cm2, range 3.85-11.89 IU/cm2, p = 0.14, n = 10) was not significantly reduced when compared to the initial activity (median 8.74 IU/cm2, range 2.22-17.68 IU/cm2, n = 10). After 30-50 minutes CPB the PAA was significantly reduced (median 3.93 IU/cm2, range 1.5-13.24 IU/cm2, p = 0.028, n = 10) and still reduced after rewarming for 10 minutes (median 3.12 IU/cm2, range 0.88-19.93 IU/cm2, p = 0.047, n = 10). The simultaneous plasma tissue-type plasminogen activator activity showed a significant (p < 0.05) increase after 30-50 minutes bypass with a later decline. The changes in the reoperative pericardial PAA were similar. In addition, the degree of PAA in reoperative pericardium was consistently lower than that observed in primary tissue. The extent of primary pericardial mesothelial damage at times B, C, and D compared with that at time A showed a significant (p < 0.01 for times B, C, and D) increase. Similarly there was a significant worsening of the degree of inflammation. Compared with primary pericardium, the reoperative samples showed a significant (p < 0.01 for times A, B, and C) preponderance of damaged mesothelium at the earlier stages of the operation. It appears that, following the initial bypass surgery, the processes that cause pericardial and mesothelial healing with recovery of PAA compete with those leading to pericardial adhesions and fibrosis. The histological and biochemical outcome seen in reoperative pericardium is the result of these competitive actions.