Postoperative cardiac, pulmonary, renal and coagulation dysfunction, along with C3a levels, were studied prospectively in 116 consecutive patients undergoing open cardiac operations and 12 patients undergoing closed operations in the same time period. The level of C3a 3 hours after open operation was high (median value 882 ng X ml-1 plasma) and was related to the C3a level before cardiopulmonary bypass (CPB) (p = 0.03), the level at the end of CPB (p less than 0.0001), elapsed time of CPB (p = 0.07), and older age at operation (p less than 0.0001). It was inversely related to the cardiac output as reflected by the strength of the pedal pulses (p = 0.006). In contrast, C3a levels did not rise in patients undergoing closed operations. The probability of postoperative cardiac dysfunction after open operations (present in 27 of 116 patients) was predicted by C3a levels 3 hours after operation (p = 0.02), the CPB time (p = 0.02), and younger age (p less than 0.0001). The same risk factors pertained for postoperative pulmonary dysfunction (present in 41 of the 116 patients); renal dysfunction (present in 24 of the 116 patients) except that CPB time was not a risk factor here; abnormal bleeding (present in 21 of the 116 patients); and important overall morbidity (present in 26 of 116 patients). As regards important overall morbidity, the C3a level effect became evident at about 1,900 ng X ml-1 (a level reached by 9% of patients); the effect of increasing time of CPB became evident at about 90 minutes of CPB time; and the effect of young age became evident as age decreased from 10 to 4 years. This study demonstrates the damaging effects of CPB, relates them in part to complement activation by the foreign surfaces encountered by the blood, and supports the hypothesis that the mechanisms of the damaging effects include a whole-body inflammatory reaction.