Although echocardiography has proved useful in detecting mitral valve prolapse, its limitations have not yet been adequately defined. This study was designed to evaluate the prevalence of false negative echocardiograms in patients with angiographically proved mitral valve prolapse. Twelve patients, eight men and four women with a mean age of 47 years, were selected on the basis of the results of cardiac catheterization for chest pain. Each patient had moderate to severe mitral valve prolapse, confirmed angiographically by two observers, with no coronary artery disease or other detectable cardiac abnormalities. Clinically, a systolic click was detected in three patients, a mid-systolic murmur in five, an abnormal electrocardiogram in four and a positive maximal treadmill stress test in two of eight tested. Left ventricular angiograms exhibited anterior and posterior leaflet prolapse in five, and posterior leaflet prolapse alone in seven. High quality echocardiograms were obtained in 11 patients; one record of inadequate quality was excluded. The echocardiograms revealed mitral valve prolapse in only one case, and were "probably" negative in two, and clearly negative in eight. Although these results may reflect the well recognized variable clinical expression of this syndrome, they indicate that false negative echocardiograms are common in this selected older population of patients with angiographic mitral valve prolapse who present with chest pain and few other clinical features. Thus, caution must be exercised in the clinical interpretation of a single echocardiogram negative for mitral valve prolapse.