Analysis of the rate-related change in exercise-induced ST segment depression, the ST/HR slope, has been shown to significantly improve the accuracy of the exercise ECG for the identification of patients with coronary artery disease and for the recognition of patients with stable angina pectoris who have anatomically or functionally severe coronary artery obstruction. This method, in effect, normalizes the extent of ST segment depression for heart rate, which serves as an index of exercise-induced augmentation of myocardial oxygen demand. While preserving the specificity of the exercise ECG at greater than 90%, an ST/HR slope value of 1.1 microV/bpm as an upper limit of normal improved exercise test sensitivity from 57% to 91% in patients with stable angina who were examined using standard Bruce protocols and three monitoring leads. In addition, an ST/HR slope value of 6.0 microV/bpm was found to partition patients with and without three-vessel coronary artery disease with a sensitivity of 78%, specificity of 97%, positive predictive value of 93%, and overall test accuracy of 90%. No other criteria based on standard ECG interpretation performed as well as the ST/HR slope for the recognition of three-vessel disease in these patients. Further, patients with high ST/HR slopes who did not have three-vessel coronary disease could be shown to have functionally severe two-vessel disease by radionuclide cineangiography. These data suggest that the ST/HR slope can improve the evaluation and management of patients with possible coronary disease. Additional improvement in ST/HR slope accuracy and applicability is likely to result from modification of exercise protocols to reduce heart rate increments between stages, an increase in monitoring leads to include CM5, and computer analysis of the ST segment depression.