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Patients received a calculated dose of protamine at two different rates (5 min and 30 min) after coronary artery surgery to determine the relationship of the rate of protamine administration with the adequacy of heparin reversal and the rate of return of antithrombin III (AT III) activity. Plasma heparin concentrations and AT III activities were measured at specific times both during and for 3 days after cardiac surgery. Both rates of protamine administration resulted in clinically acceptable clotting, return of the activated coagulation time to normal, and zero heparin concentration after 24 hr. Two hours after protamine administration, patients who received rapidly administered protamine had prolonged coagulation compared to the other group. Normal AT III activity returned the second postoperative day. These results imply that normal postoperative coagulation occurs when protamine is administered over 30 min without a bolus, and that blood is potentially hypercoagulable immediately after heparin reversal because of depressed AT III activity.