Although coronary vasospasm can contribute to the development of unstable angina, the definite diagnostic method has not been established. The purpose of this study was to determine if ergonovine echocardiography (detection of regional wall motion abnormality during bedside ergonovine challenge) after angiographic confirmation of insignificant fixed disease would be useful and safe in detecting coronary vasospasm in patients with unstable angina. After control of chest pain with medications in patients admitted to the coronary care unit under the tentative diagnosis of unstable angina, diagnostic coronary angiography was performed. All patients with normal or insignificant fixed disease underwent ergonovine echocardiography after discontinuation of medications for 4+/-1 days. Among 208 consecutive patients enrolled for this study, 75% (156 of 208) showed significant fixed disease in the angiography. Ergonovine echocardiography was performed in 52 patients with insignificant disease, and coronary vasospasm was documented in 33 (63%, 33 of 52). No serious procedure-related arrhythmia or myocardial infarction occurred. Esophageal motility disorder and hypertrophic cardiomyopathy were diagnosed in 6 and 3 patients, respectively. Chest pain of undetermined etiology was the final diagnosis at discharge in 10 patients (5%, 10 of 208); among them chest pain redeveloped in 2 patients, and repeated ergonovine echocardiography revealed positive results. Our data suggest that among patients with the clinical presentation of unstable angina, coronary vasospasm is the main cause of myocardial ischemia in a considerable number of patients with a normal or near-normal angiogram, and ergonovine echocardiography after confirmation of absence of significant fixed disease is useful and safe for noninvasive diagnosis of coronary vasospasm in this setting.