We have studied the effect of the number and ordering of exercise electrocardiographic (ECG) leads when using the maximum value of the ST segment depression/heart rate (ST/HR) hysteresis over a different number of leads for the detection of coronary artery disease (CAD). The study population consisted of 127 patients with CAD and 220 patients with a low likelihood of the disease referred for an exercise test at Tampere University Hospital, Finland. The lead system used was the Mason-Likar modification of the standard 12-lead system, and exercise tests were performed on a bicycle ergometer. The number of leads was studied using lead sets consisting of first 2 leads, then 3 leads, and so on, up to all 12 leads. The criterion for the order of inclusion of the next lead in the new lead set was based on the maximized area under the receiver operating characteristic (ROC) curve for the new lead set. The importance of the number of leads was evaluated by means of three different approaches: ROC analysis; using a fixed partition criterion of 0.01 mV; and using a fixed specificity value of 80%. According to the results, the most powerful diagnostic capacity of an individual lead was in lead V5, and the most deficient diagnostic capacities were in leads aVL and V1. Using the maximum search procedure, it was possible to improve the diagnostic capacity of the ST/HR hysteresis by anything from 4 up to a maximum of 8 leads. After that it started to decrease rapidly. In conclusion, this study suggests that the diagnostic capacity of the ST/HR hysteresis could be improved by increasing the number of leads. However, the selection of leads is of major importance when using the maximum value of the ST/HR hysteresis over the leads in the detection of CAD.