It has been believed for many years that ST depression is not only a marker for ischemia, but the more severe the ST depression found during exercise, the more severe the degree of ischemia in the myocardium. This is due to the fact that ST depression becomes manifested during exercise early on and then increases in many patients as the workload increases. It has also been believed that when ST depression is present in multiple leads, it is associated with more severe ischemia than when it only occurs in a single lead. This concept has recently been challenged by a report that patients with 2 mm of ST depression did not have any quantitatively different thallium scans than those with 1 mm of ST depression. Thus, it would appear that the time-honored concept, which has rarely been documented in the literature, needs to be tested systematically. This study was designed to determine whether the multilead ST depression (sum of ST depression in all leads, the number of leads with ST depression, and the magnitude of ST depression) can predict the number of obstructed vessels, the presence or the size of the thallium defect in myocardium and, thus, the severity of myocardial ischemia. We reviewed 138 patients in our computer file with coronary angiograms and treadmill exercise testing. We also selected 56 patients who had exercise tests and thallium scintigraphy. The ST changes were correlated with the scintigraphic data and in those with coronary angiograms with a magnitude of ischemia estimated from the coronary anatomy. Comparisons of anatomic coronary severity were based on both 1-, 2- or 3-vessel disease. Using the sum of the ST depression as a criterion we did not find a significant difference between patients with 1-, 2- or 3-vessel disease. Also, there was no differentiation in the ECG pattern on patients with scintigrams showing a large thallium defect and no defect. There was a significant difference between the sum of the ST depression in those with no disease and those with significant coronary artery disease. The study showed that: (1) the sum of ST depression in all leads, the number of leads with ST depression, and the magnitude of ST depression do not predict the number of vessels obstructed nor the presence or the size of the thallium defect. (2) The sum of ST depression in all leads, the number of leads, and the magnitude of ST depression in any lead do predict ischemia when compared to those with no disease.