Nitroglycerin (TNG) reduces ischemic injury during acute coronary occlusion in dogs with otherwise normal coronary arteries, but its effect in the presence of pre-existing multivessel coronary disease is unknown. We therefore examined the influence of TNG on acute ischemia in dogs with chronic multivessel coronary occlusions. The left anterior descending (LAD) coronary artery was acutely occluded by a balloon cuff in conscious dogs two weeks after placement of ameroid constrictors to produce gradual occlusion of the obtuse marginal and posterior descending coronary arteries. Adequacy of balloon and ameroid coronary occlusion and degree of collateralization were assessed by coronary angiography. Nitroglycerin decreased arterial pressure and increased heart rate. Myocardial ischemia, determined after LAD occlusion by summing ST-segment elevation (sigmaST) from eight intramyocardial electrodes, lessened with TNG in those six dogs whose heart rate increased less than 50 per cent, but increased in those four whose heart rate increased greater than 50 per cent. When TNG-induced change in either heart rate or arterial pressure was prevented by adding methoxamine, sigma ST was diminished even more (avg decrease 25 per cent; P smaller than 0.05). We conclude that, in the presence of pre-existing multivessel coronary occlusions, 1) TNG reduces ischemic injury during experimental acute coronary occlusion provided arterial pressure and heart rate responses are not excessive and 2) uniform improvement occurs when pressure and rate responses are abolished by an alpha-adrenergic agonist. Although results in animal studies must be extrapolated to the clinical situation with caution, these findings suggest that a similar pharmacologic approach might be applicable to the treatment of acute myocardial infarction in man, even in the presence of multivessel disease.