The cardiovascular effects of protamine were studied in 19 men with normal left ventricular function undergoing primary myocardial revascularization. Protamine was given over 120 sec after termination of cardiopulmonary bypass. Arterial and pulmonary pressures, aortic blood flow, central venous pressure, heart rate and electrocardiogram were continuously registered. Pulmonary capillary wedge pressure was recorded at the times of maximal hemodynamic response. The systolic arterial pressure fell from 116 to 66 mmHg about 60 sec after the start of protamine infusion, but spontaneously began to rise after a few seconds, reaching 90% of pre-protamine levels at 126 sec. No inotropic drugs or volume infusion were given. At about 2 min, the mean pulmonary artery pressure rose from 16.3 to 26.2 mmHg and the central venous pressure from 7.0 to 11.4 mmHg. The heart rate and cardiac output were almost unchanged throughout. Systemic hypotension and pulmonary hypertension are suggested to represent true side effects of protamine or protamine/heparin complex. When left ventricular function is good, the hypotension reverses without treatment. Volume infusion may indeed precipitate right heart failure when the pre-load effect is added to the subsequent protamine-induced pulmonary hypertension.