The 12-lead electrocardiogram in 23 patients with an evolving first myocardial infarction (12 anterior and 11 inferior) was correlated with the myocardial area at risk measured by tomographic perfusion imaging with technetium-99m sestamibi. Of several electrocardiographic factors, only the extent and quantity (with and without R-wave normalization) of ST depression differed significantly between inferior and anterior evolving infarction. The myocardial area at risk was greater in anterior than in inferior evolving infarction. The extent of the myocardium at risk correlated modestly (r = 0.58) with total ST displacement in anterior evolving infarction and with total ST depression normalized to the R wave (r = 0.70) in inferior evolving infarction. Because of the large standard errors (9 to 15% of the left ventricle), estimates of the myocardial area at risk based on these electrocardiographic variables have minimal clinical value in the individual patient.