We developed a canine model with coronary stenosis produced by intraluminal obstruction with a micro-balloon occluder to assess the role of vasomotor tone of a large coronary artery with a preexisting fixed stenosis in the genesis of myocardial ischemia. Hemodynamic and electrocardiographic responses to ergonovine, an agent capable of provoking coronary spasm, were evaluated. In the absence of coronary stenosis, intracoronary infusion of 4 micrograms/min ergonovine had no systemic and coronary hemodynamic effects. Similarly, with various degrees of external obstruction created by a screw-type metal constrictor, ergonovine had little hemodynamic effects. By contrast, with a stenosis greater than 28.4 +/- 5.0 mmHg in pressure gradient, created by intraluminal obstruction which preserved active arterial vasomotion, ergonovine-induced vasoconstriction produced a marked decrease in coronary blood flow and distal coronary pressure, followed by ST-elevation. These deleterious effects of ergonovine on coronary hemodynamics were reversed completely by intracoronary infusion of nitroglycerin. Our results indicate that the effects of normal coronary arterial vasomotor activity on a stenosed vessel can cause myocardial ischemia.