In patients undergoing exercise thallium-201 myocardial scintigraphy, activity in the inferior wall on anterior images may appear diminished when the standard supine view is used, but normal when the view is acquired with the patient upright. To determine the clinical significance of this observation, the distribution of thallium-201 activity was semiquantitatively assessed in supine and upright anterior images obtained immediately after exercise in 93 patients (65 men, 28 women). The presence of inferior wall and coronary artery disease was established with coronary angiography or from documentation of previous myocardial infarction. Supine and upright images were compared with use of receiver operating characteristic curves. In male patients diagnostic accuracy for identification of both inferior wall and coronary artery disease was improved through the use of the upright anterior image. In women, there was no significant difference in reader performance with upright and supine images. Upright anterior images should be routinely obtained in men in order to reduce the frequency of false-positive identification of inferior wall defects.