To determine whether regional myocardial ischemia plays a role in patients with the mitral valve prolapse syndrome, we examined myocardial perfusion with exercise stress testing and thallium-201 myocardial scintigraphy. Twelve patients were studied, 11 women and one man aged 18 to 56 years, mean age 30 years. In all patients, mitral valve prolapse was documented by echocardiography or phonocardiography. Patients over 35 years of age underwent cardiac catheterization. Electrocardograms disclosed abnormalities during maximal exercise in eight of the 12 patients. In two patients, angina developed during exercise. Thallium-201 (201Tl) scintigrams were normal in the 11 patients with presumed or documented normal coronary arteries. One patient, in whom an apical defect was demonstrated on scintigraphy, had significant disease of the left main and left anterior descending coronary artery. Repeat testing after successful aortocoronary bypass grafting revealed improved exercise capacity and a normal 201Tl myocardial scintigram. The data indicate that patients with mitral valve prolapse alone do not have regional myocardial ischemia and that the presence of a defect on 201Tl myocardial scintigraphy following maximal stress testing would suggest the existence of concomitant coronary artery disease.