The clinical utility of exercise thallium-201 single photon emission computed tomography was investigated in 360 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps. Sensitivity for detecting coronary artery disease was comparably high using quantitative and visual analysis, although specificity tended to improve using the former method (87% versus 76%, p = 0.09). Quantitative analysis was superior to the visual method for identifying left anterior descending (81% versus 68%, p less than 0.05) and circumflex coronary artery (77% versus 60%, p less than 0.05) stenoses and detected most patients (92%) with multivessel coronary artery disease. Multivessel involvement was correctly predicted in 65% of the patients with more than one critically stenosed vessel. Exercise variables in patients with significant coronary artery disease were similar whether the tomographic images were normal or abnormal. However, patients with coronary stenoses and normal versus abnormal tomograms had a trend toward more single vessel disease (79% versus 62%, p = 0.07) and moderate coronary stenosis (66% versus 28%, p less than 0.001), but had less proximal left anterior descending artery involvement (8% versus 34%, p = 0.05). Computer-quantified perfusion defect size was directly related to the extent of coronary artery disease. Intra- and interobserver agreement for quantifying defects were excellent (r = 0.98 and 0.97, respectively). In conclusion, quantitative thallium-201 tomography offers improved detection of coronary artery disease, localization of the anatomic site of coronary stenosis, prediction of multivessel involvement and accurate determination of perfusion defect size, while maintaining a high specificity. Quantification of perfusion defects with single photon tomography may become important for assessing the effects of coronary reperfusion and prognostically stratifying patients with coronary artery disease.