A hemodynamic study of men undergoing elective coronary artery bypass surgery was undertaken to elucidate the side effects of protamine given into the ascending aorta (group A, n = 16) or into the central venous line (group V, n = 16). After termination of extracorporeal circulation, protamine was infused over 120 seconds, and the hemodynamic profile was continuously recorded. During the first minute, the systemic arterial pressure fell to about 60% of the preprotamine level in both groups, but the hemodynamic changes occurred more rapidly (p < 0.05) in group V than in group A, with maximal pressure drop at 61.7 +/- 2.7 vs 74.4 +/- 4.9 seconds. Following spontaneous restoration of the systemic blood pressure, the pulmonary artery pressure rose considerably in both groups, as did the pulmonary capillary wedge and central venous pressures, reaching higher levels in the intravenous group. The cardiovascular responses were again more rapid in group V than in group A (p = 0.004). The degree of systemic hypotension thus did not benefit from use of the intraaortic rather than the intravenous route for administering protamine. The more pronounced and more rapid pulmonary circulatory changes in the intravenous group suggest that the hemodynamic effects of protamine are initiated in the lungs.