The objective of the study was to investigate a proposed linear relationship between the extent of myocardial ischemic injury and the ST-segment/heart rate (ST/HR) slope by computer simulation of the injury sources arising in exercise electrocardiographic (ECG) tests. The extent and location of the ischemic injury were simulated for both single- and multivessel coronary artery disease by use of an accurate source-volume conductor model which assumes a linear relationship between heart rate and extent of ischemia. The results indicated that in some cases the ST/HR slope in leads II, aVF, and especially V5 may be related to the extent of ischemia. However, the simulations demonstrated that neither the ST-segment deviation nor the ST/HR slope was directly proportional to either the area of the ischemic boundary or the number of vessels occluded. Furthermore, in multivessel coronary artery disease, the temporal and spatial diversity of the generated multiple injury sources distorted the presumed linearity between ST-segment deviation and heart rate. It was concluded that the ST/HR slope and ST-segment deviation of the 12-lead ECG are not able to indicate extent of ischemic injury or number of vessels occluded.