The effect of neurogenic coronary vasomotor tone upon contraction in ischemic myocardium was investigated in awake, mongrel dogs. The animals were chronically instrumented with a hydraulic occluder around the left circumflex coronary artery; a small catheter was also implanted within the vessel. Ultra-sound crystal pairs were placed distal to the occluder in myocardium perfused by the left circumflex artery. Pacing electrodes were sutured onto the right ventricular conus. During the experiment (n = 6) the occluder was inflated to stenose the vessel; the imposition of cardiac pacing (210/min) in conjunction with this stenosis resulted in depressed contraction of the myocardium distal to the occluder as assessed by the ultra-sound crystals: Segmental shortening decreased to 45.4 +/- 5.4% of unpaced control. Phentolamine, an alpha-antagonist, was then infused into the left circumflex catheter for ten minutes (0.1 mg/min) and the experiment repeated. After the alpha-blockade the combination of coronary stenosis and heart rate pacing decreased segmental shortening to only 84.6 +/- 10.1% of control, which was significantly (P less than 0.01) improved relative to the unblocked condition. In another experiment (n = 4), a less severe stenosis was imposed upon the left circumflex vessel. During pacing, muscle shortening decreased to 94 +/- 8.5% of control. Infusion of phenylephrine, an alpha-agonist, for ten minutes (0.1 mg/min) resulted in a 56.7 +/- 5.9% decrease in shortening during pacing; this was significantly greater (P less than 0.01) than the previous decrease. These data indicate that coronary alpha-adrenergic tone can significantly compromise regional myocardial function even in ischemic muscle whose coronary blood flow reserve has been exhausted.