We examined the effects of diltiazem, a calcium-entry blocker, on exercise-induced myocardial ischemia in nine conscious dogs with chronic coronary stenoses. An ameroid constrictor, Doppler flow probe, and hydraulic occluder were placed around the left circumflex coronary artery, and left ventricular pressure was measured (Konigsberg micromanometer). Pairs of ultrasonic crystals were implanted for measuring left ventricular systolic wall thickening (% delta WTh) in control (left ventricular anterior wall) and ischemic (left ventricular posterior wall) regions, and regional myocardial blood flow was measured with the microsphere method. Eighteen days (average) after surgery mean coronary blood flow velocity had decreased and reactive hyperemic flow velocity after 10 sec of coronary occlusion was markedly reduced, but % delta WTh at rest remained normal, indicating collateral development. Control treadmill exercise was performed for 3.7 min (average), and 2 hr later administration of 0.3 mg/kg diltiazem was followed by an identical exercise bout. Control exercise increased % delta WTh in the normal region, while in the ischemic region % delta WTh decreased markedly and ischemia was evident (subendocardial flow, 0.29 +/- 0.12[SD] ml/min/g). After diltiazem hemodynamic and % delta WTh values at rest were not changed; during exercise the heart rate was significantly lower (204 +/- 24 vs 227 +/- 33 beats/min, p less than .01), but values for other hemodynamic measures were similar to those during the control run. % delta WTh in the control region was not changed during exercise after diltiazem, but compared with control exercise in the ischemic zone there was less dysfunction and subendocardial flow was greater. Recovery from exercise-induced dysfunction in the ischemic region occurred within 5 min, compared with over 30 min after control exercise. Thus, in a preparation of chronic coronary stenosis, the calcium-entry blocker improved the relationship between regional myocardial flow and function during exercise and led to more rapid recovery of regional myocardial dysfunction.