ABSTRACTTo investigate the mechanism of the antianginal action of diltiazem in stress-induced myocardial ischemia, we studied 12 patients with stable exertional angina and disease of the proximal left anterior descending artery by measuring great cardiac vein flow (GVCF) and calculating anterior regional coronary resistance (ARCR) during myocardial ischemia induced by atrial pacing before and after intravenous administration of diltiazem (0.25 mg/kg in a bolus dose followed by continuous infusion of 0.005 mg/kg/min). Diltiazem increased the pacing time to angina from 6.9 ± 3.5 to 10.7 + 4 min (p < .001). At peak pacing heart rate was increased after diltiazem (from 128 + 17 to 145 + 17 beats/min, p < .005), while mean arterial pressure was decreased (from 131 + 19 to 1 13 + 17 mm Hg, p < .025), leaving the double product unaltered. At peak pacing no changes were observed in GCVF (from I 15 + 46 to 1 19 + 46 ml/min, p = NS), ARCR (from 1.3 ± 0.4 to 1. 1 + 0.4 mm Hg/ml/min), or myocardial oxygen consumption of the anterior region (from 14.5 + 4.2 to 13.4 ± 4.7 ml/min). Reduction of myocardial oxygen demand plays a major role in the antianginal action of diltiazem in patients with stress-induced myocardial ischemia.