The sensitivity of the commonly used stress tests for the diagnosis of coronary artery disease was analyzed in 46 patients with significant occlusion (greater than or equal to 70% luminal diameter obstruction) of only one major coronary artery and no prior myocardial infarction. In all patients, thallium-201 perfusion imaging (both planar and seven-pinhole tomographic) and 12 lead electrocardiography were performed during the same graded treadmill exercise test and radionuclide angiography was performed during upright bicycle exercise. Exercise rate-pressure (double) product was 22,307 +/- 6,750 on the treadmill compared with 22,995 +/- 5,622 on the bicycle (p = NS). Exercise electrocardiograms were unequivocally abnormal in 24 patients (52%). Qualitative planar thallium images were abnormal in 42 patients (91%). Quantitative analysis of the tomographic thallium images were abnormal in 41 patients (89%). An exercise ejection fraction of less than 0.56 or a new wall motion abnormality was seen in 30 patients (65%). Results were similar for the right (n = 11) and left anterior descending (n = 28) coronary arteries while all tests but the planar thallium imaging showed a lower sensitivity for isolated circumflex artery disease (n = 7). The specificity of the tests was 72, 83, 89 and 72% for electrocardiography, planar thallium imaging, tomographic thallium imaging and radionuclide angiography, respectively. The results suggest that exercise thallium-201 perfusion imaging is the most sensitive noninvasive stress test for the diagnosis of single vessel coronary artery disease.