Hemodynamic responses to intravenous protamine sulfate in 40 patients were evaluated. The dose of protamine administered was calculated as adequate to reverse residual heparin as measured by the activated clotting time (ACT). Thirty patients (n = 30) received protamine at a rate of 0.5 mg/kg/min and the remainder (n = 10) received protamine at a rate of 1 mg/kg/min. Hemodynamic measurements were made before protamine, at 5-min intervals during administration, and 5 min after completion of the infusion. No statistically significant changes in cardiac output, systemic arterial blood pressure, or vascular resistance were seen when protamine was administered to patients with good left ventricular function after cardiopulmonary bypass. However, in patients with poor left ventricular function after cardiopulmonary bypass, protamine infusion was associated with systemic vasodilation that was only partially compensated for by an increase in cardiac index, resulting in a 12% decrease in mean blood pressure (P less than 0.05). Thus protamine should be administered cautiously to patients who have poor left ventricular function after cardiopulmonary bypass.