OBJECTIVES. Our aim was to evaluate the influence of a calcium channel blocking agent of the dihydropyridine group (nicardipine) on coronary vasomotion during dynamic exercise. BACKGROUND. Coronary vasomotion plays an important role in the pathophysiology of myocardial ischemia. METHODS. Twenty-nine patients with coronary artery disease were studied at rest and during bicycle exercise with the use of biplane quantitative coronary angiography. Twelve patients without pretreatment (group 1) served as control subjects. Seventeen patients (group 2) received nicardipine, either 0.2 mg by intracoronary injection (n = 9) or 2.5 mg intravenously (n = 8) before exercise. RESULTS. In the control group there was exercise-induced vasoconstriction (-29%, p < 0.001) of the stenotic segment but coronary vasodilation (+22%, p < 0.05) of the normal vessel segment. In group 2, nicardipine induced coronary vasodilation of both the normal (+16%, p < 0.001) and the stenotic vessel segment (+35%). During subsequent exercise there was some additional vasodilation of normal (+4%, p = NS) and stenotic arteries (+5%, p = NS). There was no difference between either intracoronary or intravenous nicardipine with regard to vasodilation. Application of sublingual nitroglycerin was associated with significant vasodilation of the normal vessel segment in groups 1 (+18%, p < 0.05) and 2 (+15%, p < 0.001). The stenotic vessels showed a significant increase in percent cross-sectional area after nitroglycerin in groups 1 (+12%, p = NS) and 2 (+51%, p < 0.001). Exertional angina pectoris occurred less frequently in group 2 (18%) than in group 1 (67% [p < 0.005 vs. group 2]); group 2 also had a smaller increase in mean pulmonary artery pressure (+14 vs. +21 mm Hg, p < 0.05). CONCLUSIONS. Exercise induces vasoconstriction of stenotic, but vasodilation of normal, coronary vessel segments. Intravenous and intracoronary nicardipine prevent vasoconstriction of stenotic coronary arteries during exercise and exert a significant anti-ischemic effect. The combination of two anti-ischemic drugs, nitroglycerin and nicardipine, has an additive effect on coronary vasomotion that is seen only in the stenotic vessel segment. Thus, the anti-ischemic action of nicardipine is mainly due to a primary effect on coronary vasomotor response rather than to secondary effects such as changes in loading conditions.