epsilon-Aminocaproic acid (EACA) concentrations achieved during cardiopulmonary bypass (CPB) have not been previously reported. It is unknown whether plasma concentrations reported to inhibit fibrinolysis in vitro (130 microg/mL) are achieved or whether differences in these levels relate to variability in postoperative bleeding. EACA (total intraoperative dose 270 mg/kg) was administered to 27 patients undergoing cardiac reoperation. The plasma EACA concentration was measured by using high-pressure liquid chromatography: 1) 30 min after initiation of drug administration (baseline); 2) 30 min (CPB + 30) after initiation of CPB; 3) 90 min after initiation of CPB. (CPB + 90); and 4) at cardiopulmonary bypass termination (end CPB). Plasma EACA concentrations (microg/mL, min - max, mean +/- SD) were 276-998, 593 +/- 154 at baseline; 147-527, 302 +/- 95 at CPB + 30; 112-500, 314 +/- 100 at CPB + 90; and 84-537, 317 +/- 100 at end CPB. Twenty-four-hour postoperative thoracic drainage and allogeneic red blood cell transfusions were not associated with plasma levels at any time. Although plasma EACA concentrations greater than 130 microg/mL were consistently achieved, we observed a marked variability (more than sixfold) in plasma concentrations and bleeding outcomes despite the use of a weight-based dosing regimen. This variability in drug levels appears to have little relevance to bleeding outcomes, possibly since mean plasma levels exceeded 130 microg/mL during CPB, and nearly all patients (26 of 27) achieved that target level.