Planar rest myocardial thallium-201 chloride (201Tl)/F18-fluorodeoxyglucose (FDG) imaging has been shown to distinguish between viable and non-viable tissue. Twenty-five patients (60 ± 9 years) with acute myocardial infarction were studied using this technique within 6 ± 2 days (T1) after infarction and again after 42 ± 4 days (T6). Serial assessment of wall motion with 2D-echocardiography was performed to determine the predictive value of radionuclide indices for the course of impaired regional left ventricular function. No revascularization procedure was performed. Segmental 201Tl and FDG uptake was evaluated using circumferential profiles. Echocardiographic wall motion was scored as normal, hypokinetic or akinetic. Myocardial segments were considered non-viable if a match between 201Tl and FDG uptake was present, which is a concordant reduction in 201Tl and FDG uptake (Group A). Myocardial segments were considered viable if: a mismatch was present between 201Tl and FDG uptake which was defined as a segmental FDG uptake exceeding 201Tl uptake by ≤20% in a segment with reduced 201Tl uptake (Group B); a normal FDG uptake (≤75%) was present without a mismatch pattern in a segment with reduced 201Tl uptake (201Tl < 75% of peak activity) (Group C); a normal 201Tl uptake was present in the area of wall motion abnormality (Group D). Corresponding scintigraphic images obtained at T1 and T6 were compared. Results: 51 segments were normokinetic, 37 were hypokinetic and 26 were akinetic at T1. Of the 63 segments with wall motion abnormalities at T1, 18 regions showed a match (FDG-201Tl < 20%) (Group A). Regional function improved in only one (6%) of these segments. In 19 regions a mismatch was present (FDG-201Tl ≤ 20%) (Group B) of which three (16%) showed spontaneous improvement in function (p = NS vs. matched segments), although recovery varied considerably among patients. Regional function in two segments deteriorated. In 14 regions with reduced 201Tl uptake, DFG uptake was normal (Group C) of which five (36%) were improved after 6 weeks (p < 0.05 vs. match; p = NS vs. mismatched segments). Of the 12 segments with normal 201Tl uptake (Group D), seven (58%) showed improvement in function, whereas five (42%) did not show improvement (p < 0.05 vs. match). In addition, all scintigraphically selected viable segments were grouped (Group B + C + D) and compared with the non-viable segments (Group A). The predictive value of a positive viability test for spontaneous functional improvement was 33%. The predictive value of a negative viability test for lack of functional improvement was 94%. Conclusions: Absence of residual FDG uptake shortly after infarction is associated with irreversible injury, while preservation of metabolic activity identifies segments with variable outcome. Wall motion alone is not a good indicator for the presence of viable tissue. Planar 201Tl/FDG imaging allows early identification of viable but jeopardized tissue and may help select patients who will benefit from aggressive therapy to salvage endangered myocardium.