This study examined the effect of the level of exercise on the ability of thallium-201 imaging with single photon emission computed tomography (SPECT) to detect coronary artery disease. Patients in group 1 (n = 164) achieved adequate exercise end points, defined as positive exercise electrocardiograms or ≥85% of maximal predicted heart rate. Patients in group 2 (n = 108) had submaximal exercise. The SPECT thallium-201 images showed perfusion defects in 74%, 88% and 98%, respectively, of patients with one, two and three vessel coronary artery disease in group 1, compared with 52%, 84% and 79%, respectively, of such patients in group 2 (p < 0.05). Perfusion defects showed partial or complete redistribution consistent with ischemia in 56%, 80% and 88%, respectively, of patients with one, two and three vessel coronary artery disease in group 1 compared with 35%, 58% and 56%, respectively, of such patients in group 2 (p = 0.08, < 0.03 and < 0.001, respectively). Of 58 patients with normal coronary angiograms or <50% diameter stenosis, 36 (62%) had normal SPECT images. In a separate group of 131 patients with <5% pretest probability of coronary artery disease, the specificity was 93%. The sensitivity of exercise SPECT imaging in group 1 was higher than that of ST segment depression (p < 0.001). Thus, the level of exercise affects the results of SPECT thallium imaging in the localization and evaluation of the extent of coronary artery disease and the detection of ischemia. © 1989.