Plasma activities of various (iso)enzymes were measured in patients after cardiac surgery (n = 114) and after acute myocardial infarction (n = 40). From these activities, the cumulative release of enzymes in plasma was calculated with a two-compartment circulatory model. This model was adapted to transient postoperative changes in plasma volume and similar changes in the transcapillary escape rate of proteins, observed after cardiac surgery and verified in dogs after cardiopulmonary bypass (CPB). Comparison of cumulative release of enzymes with the enzyme content of myocardium, skeletal muscle, and blood cells allows identification of the various sources of enzyme release. Cardiac injury after uncomplicated bypass surgery is only 1.5 +/- 1.5 (mean +/- SD) gram equivalents (gmEq) of myocardium, compared to a loss of 31 +/- 13 gmEq of myocardium after AMI. Peroperative hemolysis is estimated at 68 +/- 15 ml of blood. Total loss of skeletal muscle amounts to 13 +/- 10 gmEq. Some hepatic enzyme release is observed after AMI but not after surgery. Large differences in time course exist between the release of enzymes from myocardium and skeletal muscle and also between myocardial release in the surgery group and in the AMI group. The accuracy of estimations is discussed and indicated as a function of the extent of cardiac injury.