The direct negative inotropic actions of calcium channel blockers limit the use of these otherwise effective systemic and coronary vasodilators in patients with heart failure. We studied the effects of amrinone pretreatment on the dose--hemodynamic response curve of diltiazem in order to test the hypothesis that amrinone might potentiate diltiazem's positive effects in anesthetized dogs. The control group (no pretreatment, n = 6) had a typical dose-related response to diltiazem (50, 100, and 150 micrograms/kg): coronary and systemic vasodilation, increased stroke volume, and no change in myocardial work and power. Amrinone pretreatment of the study group (n = 7) altered the hemodynamic response, thus maximal systemic vasodilation and stroke volume increase at a lower diltiazem dose, a 15 to 35% increase in myocardial work and power, and more profound coronary vasodilation. We propose that amrinone, by inhibiting phosphodiesterase, potentiates diltiazem vasodilation and reflexly secreted catecholamines' actions on the heart. This positive interaction may permit effective use of lower doses of diltiazem, thus circumventing its dose-limiting direct negative effects while still profitting from beneficial peripheral, reflex, and coronary actions.