A recent report suggests that there may be advantages of intraaortic (IA) versus intravenous (IV) administration of protamine for reversal of heparin at the end of cardiopulmonary bypass. Because complete haemodynamic measurements were not performed in that study, we prospectively and randomly assessed the effects of protamine sulphate administered via either route. Patients were studied in the period immediately following cardiopulmonary bypass. Heparin, 300 units . Kg-1, plus 150 units . Kg-1 when required, was administered to keep the activated clotting time greater than 400 sec. Protamine 3 mg . Kg-1 was injected over 30 sec. intravenously in the IV group (n = 5) and into the ascending aorta in the IA group (n = 5). There was a significant decrease in arterial blood pressure (28.6 per cent) from 109.2 +/- 5.6 mmHg (S.E.) systolic to 78.0 +/- 9.0 mmHg observed in the IA group one minute post protamine, which returned to baseline by 2.5 min (analysis of variance p less than 0.05). No significant hypotension was observed in the IV group. There was no significant change in heart rate, left atrial pressure, central venous pressure, systemic vascular resistance or cardiac index with either IA or IV protamine. In contrast to our recent study in pigs there was no significant change in pulmonary artery pressure, pulmonary vascular resistance or cardiac output with protamine. Results indicate that there are no haemodynamic benefits of IA vs IV injection of protamine.