Verapamil, a calcium antagonist, has been used extensively for treatment of cardiac arrhythmias. Concern persists, however, that it may seriously depress myocardial function in cardiac patients. To investigate this possibility, 20 patients with coronary artery disease (CAD) but no heart failure were given intravenous verapamil (0.1 mg/kg bolus, followed by 0.005 mg/kg/min infusion), and studied hemodynamically and angiographically. Verapamil markedly lowered mean aortic pressure (94 ± 17 to 82 ± 13 mm Hg,p < 0.0005) and systemic vascular resistance (1413 ± 429 to 1069 ± 235 dyn-sec-cm-', p < 0.0005). Simultaneously, all indices of left ventricular (LV) performance greatly improved: cardiac index rose from 2.8 ± 0.6 to 3.1 i 0.7 1/min/m2 < 0.0005), mean velocity of circumferential fiber shortening increased from 0.85 ± 0.39 to 0.97 ± 0.46 circ/sec (p < 0.01), and ejection fraction improved from 55 ± 16 to 61 ± 18% (p < 0.01). No significant changes were noted in the heart rate before and after verapamil administration, and verapamil did not worsen the extent of LV asynergy in the majority of patients. In patients with CAD, the intrinsic negative inotropic effect of verapamil is of negligible importance because its potent vasodilatory properties more than compensate for any intrinsic decrease in LV contractility, and thereby improve the overall cardiac function.