In many patients with coronary artery disease (CAD), impaired left ventricular (LV) function arises on the basis of regionally ischemic or hibernating myocardium rather than irreversibly infarcted myocardium. However, the identification of such potentially irreversible LV dysfunction has been problematic. Many exercise-induced thallium-201 defects do not normalize on subsequent resting redistribution images, even when the underlying myocardium is viable. We have demonstrated that reinjection of Tl-201 at rest immediately after the standard 4-hour redistribution image facilitates late uptake of Tl-201 and distinguishes between viable and infarcted myocardium. We studied 100 patients with chronic CAD. Of 260 abnormal myocardial segments during exercise, 85 (33%) were irreversibly abnormal on the redistribution study. However, 42 of these defects (49%) demonstrated improved or normal uptake after TI-201 reinjection. That the late uptake of Tl-201 after reinjection represents viable myocardium is substantiated in 3 subgroups of patients. 1) In 20 patients restudied 3-6 months after revascularization, improved wall motion and improved blood flow was observed in 87% of segments with "irreversible" defects on redistribution studies identified as viable by Tl-201 reinjection before revascularization; such improvement occurred in no segment identified as scar. 2) In 12 patients studied by magnetic resonance imaging, segments identified as viable by this method had a normal degree of systolic wall thickening, significantly greater than the regions identified as scar. 3) In 16 patients studied by PET imaging with 18F-fluorodeoxyglucose (FDG), segments with TI-201 defects identified as viable by reinjection had metabolic evidence for myocardial viability. The concordance between the Tl-201 reinjection and FDG uptake data was excellent, with 51% of regions with severe "irreversible" defects identified as viable by both techniques. These data indicate that Tl-201 reinjection is a convenient and relatively inexpensive method to identify viable myocardium in patients with chronic CAD and LV dysfunction.