To determine the relative contributions of milrinone's positive inotropic and vasodilator actions in patients with severe congestive heart failure, the drug was administered by constant infusion directly into the left main coronary artery of 11 patients with New York Heart Association functional class III or IV heart failure. Intracoronary infusion of milrinone at rates up to 50 μg/min had no effect on mean arterial pressure or systemic vascular resistance but resulted in dose-related increases in peak positive dP/dt (+ 21%), stroke volume index (+ 18%), and stroke work index (+ 21%) and decreases in heart rate (−33%), mean right atrial pressure (− 25%), and left ventricular end-diastolic pressure (− 17%). In eight patients, intravenous administration (75 jig/kg) after the intracoronary infusion resulted in significant decreases in mean arterial pressure (− 14%) and systemic vascular resistance (40%), further increase in stroke volume index compared with intracoronary administration, further decreases in mean right atrial and left ventricular end-diastolic pressures compared intracoronary administration. These data indicate that milrinone exerts both positive inotropic vasodilator actions that contribute significantly to the drug's overall hemodynamic effect.