BACKGROUND Acute depletion of plasma fibronectin levels has been reported during and after cardiopulmonary bypass; degradation of fibronectin by proteolytic enzymes has been suggested as one of the causes. This study was designed to assess the possible preservation of fibronectin levels by aprotinin during cardiopulmonary bypass. METHODS Plasma fibronectin levels were evaluated in 19 patients undergoing either elective coronary artery bypass grafting or a valvular heart operation. The study was conducted prospectively in a controlled, randomized, double-blinded manner. Nine test patients (group A) received intraoperative, intravenous administration of aprotinin; 10 control patients (group B) received equivalent volume of normal saline solution. Fibronectin levels were measured immediately after induction of anesthesia (as the baseline for the study) and at the following times: after 5 minutes on bypass, after 30 minutes on bypass, immediately before the start of rewarming, and after being off bypass for 5 minutes, but before protamine administration. RESULTS Both groups' basic characteristics were very similar. Group A patients were found to have significantly greater fibronectin levels than group B during and immediately after cardiopulmonary bypass (p < 0.002). CONCLUSIONS Administration of aprotinin intraoperatively appears to result in better preservation of fibronectin levels during cardiopulmonary bypass. Although the mechanism of action of aprotinin as a proteolytic inhibitor remains unclear, it has been suggested that it exerts an inhibiting effect on proteolytic enzymes by forming an aprotinin-proteinase complex. The clinical implications of the greater level of fibronectin achieved by the intraoperative use of aprotinin during cardiopulmonary bypass need further evaluation.