The relation between the quantitative myocardial perfusion defect severity of exercise thallium-201 single-photon emission computed tomography (SPECT) and the quantitative degree of coronary stenosis was examined in 18 patients with 1-vessel disease (≥50% diameter stenosis), and abnormal thallium-201 SPECT. A total of 26 vessels were analyzed. Thallium-201 SPECT quantitative defect severity score was derived by summing the number of pixels in a coronary territory in which counts fell below the normal mean and multiplied by the number of SDs by which they fell below the normal mean. The thallium-201 defect severity score was significantly (p < 0.001) related to the maximal percent luminal diameter narrowing (r = 0.93), percent area narrowing (r = 0.89), absolute stenotic area (r = 0.79), and absolute stenotic diameter (r = 0.81). As expected, the strongest relation between thallium-201 defect severity and quantitative angiographic indexes was in the low and high ranges of coronary stenosis, with more variability and lower correlation coefficients (percent diameter r = 0.75, p < 0.02, percent area stenosis: r = 0.63, p < 0.05) in the middle ranges (50 to 80% diameter stenosis). This observation is likely to be due to the complex flow characteristics across stenotic lesions. The findings suggest that in a select population, thallium-201 defect severity is potentially useful for noninvasive characterization of the functional severity of coronary artery stenosis and may complement coronary angiography in predicting functionally significant stenosis.