Preliminary studies have suggested that QRS-amplitude changes due to exercise-induced alterations in ventricular volume and function can improve the diagnostic value of the exercise test. To evaluate this, electrocardiographic data and equilibrium radionuclide angiographic images were recorded simultaneously in 18 normal subjects and 60 coronary artery disease patients at rest and during supine bicycle exercise. In 24 of the 60 coronary artery disease patients, left ventricular volumes were also calculated. The measured QRS amplitudes were the R waves in V5, X, Y and Z, the Q wave in Z and the sum of amplitudes of R waves in X and Y and the Q wave in Z (ΣR). The mean left ventricular ejection fraction increased significantly from rest to peak exercise in the normal subjects; however, the mean left ventricular ejection fraction and mean volumes did not change significantly in the coronary patients. There was no significant differences in the mean QRS-amplitude changes during exercise between the coronary artery disease patients and the normal subjects in any of the measured leads. The sensitivity and specificity of exercise-induced QRS-amplitude changes for coronary disease were lower than ST-segment changes. For ST-segment changes, the sensitivity was 57% and specificity was 100%; the best sensitivity and specificity for QRS amplitude occurred in RZ, 48% and 67%, respectively. When ejection fraction was related to ΣR at rest and peak exercise for both normal subjects and coronary patients the correlations were fair (0.50, 0.51 respectively); however, the correlation between the magnitude of ΣR and ejection fraction from rest to peak exercise was poor and did not improve with any other measured QRS amplitudes or by separating normal subjects from coronary patients with and without previous myocardial infarction. There were also poor correlations between end-diastolic and end-systolic volumes to QRS amplitudes at rest, peak exercise and their magnitude of change from rest to peak exercise. thus, R-wave amplitude changes during exercise testing have little diagnostic value and are not related to exercise-induced changes in left ventricular function of volumes.