To examine the effect of milrinone on myocardial energetics in patients with congestive heart failure, we measured systemic, pulmonary, and coronary hemodynamics in 18 patients before and after intravenous administration of milrinone (125 +/- 36 micrograms/kg). There was a 45% increase in cardiac index (2.1 +/- 0.5 to 3.0 +/- 0.6 liters/min/m2; p = .0001), a 39% fall in the pulmonary capillary wedge pressure (28 +/- 8 to 17 +/- 8 mm Hg; p = .0001), and a 42% increase in left ventricular external work (3758 +/- 1419 to 5340 +/- 1598 g-m/min; p = .0001). Both the heart rate-blood pressure product (9624 +/- 2272 to 9380 +/- 2428 mm Hg-beats/min; p = NS) and regional left ventricular myocardial oxygen consumption (7.6 +/- 2.9 to 8.1 +/- 3.1 ml O2/min; p = NS) were unchanged after milrinone, resulting in a 45% increase in calculated left ventricular external efficiency (p = .004). Although myocardial oxygen consumption did not change, regional great cardiac venous blood flow increased significantly (73 +/- 32 to 85 +/- 34 ml/min; p = .02) as a result of a 30% reduction in regional coronary vascular resistance (1.32 +/- 0.99 to 0.93 +/- 0.54 mm Hg-min/ml; p = .004), a decrease comparable to the concurrent 37% and 38% falls seen in systemic and pulmonary vascular resistance, respectively. These changes were associated with an 11% fall in the transcoronary arterial-venous oxygen difference (111 +/- 24 to 99 +/- 21 ml/O2/liter; p = .0001), which is consistent with a primary coronary vasodilator effect of milrinone.(ABSTRACT TRUNCATED AT 250 WORDS)