To determine the effect of isosorbide dinitrate or ischemic myocardium, this agent was administered to dogs with well developed coronary collateral vessels 8 to 14 weeks after embolization and subsequent occlusion of the left anterior descending coronary artery. After thoracotomy the left coronary artery was cannulated and perfused with blood from the femoral artery. The distal left anterior descending artery was cannulated to monitor peripheral coronary pressure. Regional contractile force in the normal left circumflex and potentially ischemic left anterior descending regions was measured with isometric strain gauge arches sewn to the epicardium. Moderate decreases in coronary perfusion pressure averaging 27 mm Hg produced selective ischemia in the myocardium beyond the site of occlusion of the left anterior descending artery. Under these conditions the average increase in peripheral coronary pressure produced by intracoronary injection of isosorbide dinitrate was 9.0 mm Hg, whereas contractile force in the ischemic region increased by 30 percent. The contractile force was unchanged in the normal regions. Therefore, isosorbide dinitrate can dilate coronary collateral vessels and improve contractile force in ischemic areas. Intracoronary injection of nitroglycerin had similar effects. The durations of responses to isosorbide dinitrate and nitroglycerin were remarkably similar: 6.4 and 6.7 minutes, respectively. Although isosorbide dinitrate can directly dilate coronary collateral vessels, its effects are not longer lasting than those of nitroglycerin.