Nitroglycerin (TNG) decreases ST-segment elevation accompanying myocardial ischemia, but its effect on morphometrically and enzymatically estimated infarct size (IS) has not been defined. Accordingly, coronary occlusion was produced in 92 conscious dogs; 65 survived for 24 hours. Thirty-three received TNG (200-300 μg/min i.v. for 8 hours) and the results were compared with those in 32 untreated dogs. Coronary blood flow (CBF) was measured with tracer microspheres (141Ce, 85Sr and 95Nb) 5 minutes after occlusion before TNG, 20 minutes after TNG and again at 8 hours. Mean blood pressure decreased from 103 to 84 mm Hg with TNG, vs 99 to 94 mm Hg in controls (p < 0.02). Nitroglycerin increased CBF in the subendocardium of ischemic areas by 45% (0.09 to 0.13 ml/min/g). The dogs were sacrificed after 24 hours and IS was estimated morphometrically (25 ± 1% vs 27 ± 1%) of left ventricular weight) and from myocardial CK depletion (23 ± 1% vs 24 ± 1%) were similar for the two groups. Thus, despite increased subendocardial CBF, prolonged i.v. TNG did not decrease infarct size, although a 15% difference would have been detected with this sample size. TNG may relieve coronary spasm but does not appear to be beneficial with sustained coronary occlusion.