Most studies investigating the ability of exercise two-dimensional echocardiography to identify patients with coronary artery disease have included patients with left ventricular wall motion abnormalities at rest. This has the effect of increasing sensitivity because patients with only abnormalities at rest are detected. To determine the diagnostic utility of exercise echocardiography in patients with normal wall motion at rest, 64 patients were studied with exercise echocardiography in conjunction with routine treadmill exercise testing before coronary cineangiography. All 24 patients who had no angiographic evidence of coronary artery disease had a negative exercise echocardiogram (100% specificity). Nine of 40 patients with coronary artery disease (defined as greater than or equal to 50% narrowing of at least one major vessel) also had a negative exercise echocardiogram (78% sensitivity). Of the nine patients with a false negative exercise echocardiographic study, six had single vessel disease. Among 25 patients with single vessel disease, exercise echocardiography was significantly more sensitive (p = 0.01) than treadmill exercise testing alone (76 versus 36%, respectively). Among 15 patients with multivessel disease, the two tests demonstrated similar sensitivity (80%). In conclusion, exercise echocardiography is highly specific and moderately sensitive for the detection of coronary artery disease in patients with normal wall motion at rest. Although exercise echocardiography is significantly more sensitive than treadmill exercise electrocardiographic testing alone in patients with single vessel disease, the two tests are similar in their ability to detect coronary artery disease in patients with multivessel disease and normal wall motion at rest.