To evaluate whether the flow-mediated vasodilation and coronary flow reserve are impaired or not in patients with vasospastic angina (VA), we measured the changes of epicardial coronary artery diameter and flow reserve in spasm related-left anterior descending coronary artery (LAD). The flow mediated-response of epicardial coronary arteries in 15 VA were compared with 15 controls. Using quantitative coronary angiography, we measured the diameter of proximal (pLAD) and middle segment (mid-LAD) of LAD under baseline conditions, during increased blood flow after distal adenosine injection and after proximal administration of nitroglycerin. An increased fraction of average peak velocity after injection of adenosine was similar in both groups [control 340 (mean)+/-24 (SEM)%; VA 330+/-19%]. Flow-mediated vasodilation was preserved in all controls (pLAD 13.1+/-1.4%; mid-LAD 15.8+/-2.5%) but it was significantly impaired in patients with VA (pLAD -1.0+/-1.8%; mid-LAD 0.1+/-3.5%). The vasodilator response to nitroglycerin was comparable in controls (pLAD 25.8+/-2.8%; mid-LAD 27.2+/-2.8%) and VA (pLAD 26.2+/-5.2%; mid-LAD 26.7+/-3.5%). Coronary flow reserve is preserved in patients with VA. However, the flow-mediated response of spasm related-epicardial coronary artery is impaired. This may play an important role in the pathogenesis of coronary artery spasm.