As coronary angiography became more widely practiced in the 1960s, it was soon apparent that not all patients with clinical suspicion of coronary artery disease (CAD) had obstruction of epicardial coronary arteries. Several published series, including the National Heart, Lung, and Blood Institute-sponsored CASS (Coronary Artery Surgery Study) and the WISE (Women's Ischemia Syndrome Evaluation) study, have reported that up to one-half of patients undergoing coronary angiography are found to have normal or nonobstructed epicardial coronary arteries (1- 3). In 1967, Likoff et al. (4) reported on 15 women ranging in age from 30 to 53 years with chest pain despite normal coronary angiograms (CPNCA), but with electrocardiographic (ECG) abnormalities at rest (ST-segment depression or T-wave inversion) that were accentuated by exercise. Despite the ECG changes during exercise, the hemodynamic response—as assessed by pulmonary artery pressure, cardiac output, and oxygen consumption—was reported as normal in the 8 patients in whom these measurements were made. The authors of this article stated that “usual therapy of CAD was ineffective and unwarranted” in this setting (4). That same year, Kemp et al. (5) reported on a series of 50 patients (62% women) with CPNCA, commenting that as a group, “these patients may frequently have the most severe pain syndromes, often proving refractory to conventional forms of therapy.” Of the 41 patients who underwent metabolic study during isoproterenol stress, 11 showed myocardial lactate production supportive of myocardial ischemia. Of these 11 patients, 4 had ischemic-appearing ECGs during exercise stress; however, 5 additional patients with ischemic-appearing ECGs during exercise stress did not show myocardial lactate production during isoproterenol infusion. In a 1973 editorial, Kemp (6) noted that the heterogeneity of patients included in studies of patients with CPNCA makes it difficult to derive clinical or mechanistic insights about this syndrome. The term “syndrome X” was used in this editorial (based on group X in the article under discussion) to denote the uncertainty of chest pain etiology in these patients, a term subsequently used by other investigators, but often with different criteria for its definition.