Mitral leaflet prolapse syndrome has been associated with anginal chest pain, atypical chest pain, electrocardiographic abnormalities and positive stress electrocardiograms. These features overlap those of ischemic heart disease. Furthermore, coronary artery disease is frequently associated with mitral leaflet prolapse. This study evaluated the usefulness of stress myocardial scintigraphy in distinguishing these two disorders. Thirty-two patients with an angiographic diagnosis of mitral leaflet prolapse were studied. Of the 22 patients (8 men and 14 women, mean age 48 years) with a normal coronary arteriogram, 5 had "typical" angina pectoris, 6 had resting electrocardiographic abnormalities and 6 had a positive stress electrocardiogram; all 22 patients had a normal stress myocardial scintigram. Of the 10 patients (7 men and 3 women, mean age 55 years) with at least 70 percent stenosis of one coronary artery, 6 had "typical" angina pectoris, 1 had resting electrocardiographic abnormalities and 7 had a positive stress electrocardiogram. Nine of these 10 patients had one or more demonstrable perfusion defects on stress myocardial scintigrams. It is concluded that mitral leaflet prolapse syndrome is not associated with regional myocardial ischemia as demonstrated with stress scintigraphy, and that stress scintigraphy, a noninvasive technique, is useful in distinguishing the mitral prolapse syndrome from mitral prolapse associated with coronary artery disease.