Rest technetium-99m sestamibi single-photon emission tomography (SPET) has been shown to underestimate viability in some patients with chronic ischaemic myocardial dysfunction. The present study was designed to appraise the value of 99mTc-sestamibi as a viability tracer in patients with a recent myocardial infarction and to determine factors that might influence its accuracy in assessing infarct size. Therefore, rest 99mTc-sestamibi SPET, low-dose dobutamines stress echocardiography and quantitative coronary angiography were performed in 51 patients with a recent myocardial infarction. Perfusion activity and regional wall motion were scored semi-quantitatively using the same segmental division of the left ventricle. Assessment of 99mTc-sestamibi uptake as a marker of viability was performed by comparing a binary uptake score (viable=>50% vs necrotic =</=50% of the maximal tracer activity) with a binary wall motion classification during low-dose dobutamine infusion (viable=normal/hypokinetic vs necrotic=akinetic/dyskinetic). Infarct size, expressed as the number of segments with evidence of necrotic tissue, was significantly greater in the scintigraphic study than in the echocardiographic study (2.8+/-1.5 vs 2.2+/-1.3, P=0.006). This overestimation of infarct size by 99mTc-sestamibi was present only in patients with a severe infarct-related stenosis (% diameter stenosis >/=65%-100%) and particularly those with "late" reperfusion therapy (time delay >/=180 min). In patients without a severe infarct-related stenosis, 99mTc-sestamibi was able to accurately distinguish viable from necrotic segments. Thus, rest 99mTc-sestamibi scintigraphy early after acute myocardial infarction may underestimate residual viability within the infarct region, particularly in patients with low flow state coronary anatomy, as a result of a severe infarct-related stenosis and/or late reperfusion therapy.