The clinical features of mitral valve prolapse syndrome and ischemic coronary disease overlap, making differentiation of the two conditions difficult. Furthermore, many patients have both conditions. This study assessed changes in ventricular function during rest and exercise in patients with mitral valve prolapse alone and in patients with prolapse and concomitant coronary artery disease. Twelve patients with angiographically documented mitral valve prolapse and normal coronary anatomy and 11 patients with normal coronary anatomy and no mitral valve prolapse had increased ejection fraction and demonstrated no wall motion abnormality during exercise. Changes in ventricular function during exercise in 11 additional patients with mitral valve prolapse demonstrated on echocardiography were similar to those in the group with mitral valve prolapse and normal coronary anatomy seen on angiography. In contrast, 6 of 11 patients with mitral valve prolapse and coronary arterial stenosis demonstrated on angiography had a decreased ejection fraction and exhibited wall motion abnormalities during exercise. These results suggest that mitral valve prolapse alone has no detrimental effect on ventricular function during rest and exercise and that exercise-induced abnormalities in ventricular function are related to the presence and severity of coronary artery disease and not to mitral valve prolapse.