The effect of cardiac sympathetic blockade by high thoracic epidural anesthesia (TEA) (T1-T6, bupivacaine) on the luminal diameter of normal and diseased portions of epicardial coronary arteries was determined by quantitative coronary angiography in patients (n = 27) with severe coronary artery disease (CAD). In a separate group of patients (n = 9) with severe CAD, the effects of TEA on coronary arterioles (resistance vessels) were studied, by measuring total and regional myocardial blood flow and metabolism with the retrograde coronary sinus thermodilution technique. At the stenotic segments, TEA induced an increase in luminal diameter from 1.34 ± 0.11 to 1.56 ± 0.13 mm (P< 0.002), but did not change the diameter of the nonstenotic segments (3.07 ± 0.13 to 2.99 ± 0.13 mm). In the second group of patients, TEA induced no changes in coronary perfusion pressure, total or regional myocardial blood flow, coronary venous oxygen content, coronary blood flow distribution, regional myocardial oxygen consumption, or lactate extraction or uptake. Two patients had chest pain in the control situation and had regional myocardial lactate production that was attenuated by TEA. We conclude that TEA may increase the diameter of stenotic epicardial coronary artery segments in patients with CAD without causing a dilation of coronary arterioles. These effects may be beneficial when high TEA is used to treat severe ischemic chest pain in patients at rest.