Myocardial thallium-201 (Tl-201) imaging performed in conjunction with exercise stress has enhanced the accuracy of detecting coronary artery disease among patients with chest pain. Sensitivity and specificity of qualitative visual Tl-201 scintigraphy for detection of coronary artery disease average 84% and 87%, respectively. Quantitative analysis of planar Tl-201 scintigrams has yielded sensitivity and specificity in the 90% range. Single photon emission computed tomographic imaging is associated with even higher sensitivity but with specificity in the 82-85% range. Perfusion defects representing ischemia can now be distinguished from scar by demonstration of delayed Tl-201 redistribution or enhanced uptake after reinjection of a second dose of Tl-201. Stenoses of the left circumflex coronary artery are less easily detected than lesions of the right and left anterior descending coronary arteries. False-positive Tl-201 perfusion defects may occur as a result of attenuation artifacts, most often caused by overlying breast tissue or by a high left hemidiaphragm. Patient motion during acquisition of single photon emission computed tomographic images results in artifactual defects on reconstruction. Abnormal Tl-201 uptake has been noted in patients with 1) left bundle branch block and normal coronary arteries, 2) hypertrophic cardiomyopathy, and 3) progressive systemic sclerosis.