The effect of sublingual or intracoronary nitroglycerin (NTG) on luminal caliber in normal and diseased portions of epicardial coronary arteries was determined in 85 lesions from 57 typical patients with ischemic heart disease. Measurements were made from coronary angiograms, using a computer-assisted method and a carefully blinded protocol for analysis of the pre- and post- NTG angiograms. Luminal area in the "normal" portion of the diseased segment and at its maximum constriction and an estimate of flow resistance in the stenosis were computed. Luminal area increased 1.27 mm2 (p less than 0.001) in the "normal" regions, an average increase of 18% over the control area. Dilation with NTG depended strongly on vessel size; area increased 35% in normal vessels of 1.6-2.3 mm luminal diameter and only 9% in vessels 4.0-5.0 mm in diameter. Lesions were grouped into four levels of severity by percent stenosis. Minimum luminal area increased 0.35 mm2 (p less than 0.01) at the narrowest point in moderate lesions, a 22% area increase, and 0.14 mm2 (p less than 0.001) in severe lesions, a 36% area increase. Stenosis dilation resulted in an average 25% reduction (p less than 0.01) in estimated stenosis flow resistance in moderate lesions and a 38% reduction (p less than 0.001) in severe lesions. A statistically significant resistance reduction of greater than 20% occurred in 15 to 20 severe stenoses; only two of 20 showed no measurable dilation. We reviewed recent literature on hemodynamic responses to NTG and determined that changes of this magnitude are among the largest reported. We conclude that vasodilation of epicardial coronary stenosis is usually a major component of the beneficial response to NTG. We support that conclusion by demonstrating a striking improvement in ischemic left ventricular compliance abnormalities after low-dose intracoronary NTG.