Antithrombin inhibits VIIa when bound to cellular tissue factor in the presence of heparin. VIIa concentrations increase within the surgical field during cardiopulmonary bypass surgery but decrease when measured in the patient. Using a new ELISA (Stago, Reading, UK), we measured VIIa–antithrombin complexes in patients undergoing cardiopulmonary bypass to determine whether antithrombin plays a physiological role in VIIa inhibition during cardiac surgery. Samples were taken from 13 adult patients undergoing cardiac surgery with cardiopulmonary bypass at the following time points: presurgery, postheparin, 20 min intervals during cardiopulmonary bypass and postprotamine. The presurgery concentrations of VIIa–antithrombin complexes were median of 52.7pm, and these rose postheparin bolus to a median of 110pM that was maintained throughout cardiopulmonary bypass and postprotamine administration. There is an approximate twofold increase in measurable VIIa–antithrombin complexes in patients undergoing cardiac surgery, which is apparent after heparin administration. Antithrombin appears to play an active role in VIIa inhibition during cardiac surgery.