The purpose of this study was to determine the relationship of changes in the severity and extent of hypoperfusion on serial tomographic 99mTc-sestamibi images with patency of the infarct related artery during acute myocardial infarction. We studied 109 patients with acute myocardial infarction using tomographic 99mTc-sestamibi imaging acutely and at 18-48 hr later. Perfusion defect extent and defect area, an index of defect severity, were measured on both studies. Both defect extent and defect area were significantly (p = 0.0001) greater for anterior infarctions than for inferior and lateral infarctions. By two factor analysis of variance, the change in defect area varied significantly with both infarct location (p = 0.0001) and patency of the infarct-related artery (p = 0.002). The change in defect extent also varied significantly with both infarct location (p = 0.0001) and with patency of the infarct-related artery (p = 0.004). In patients with inferior myocardial infarction, a change in defect extent or defect area of greater than 4% or 0.017, respectively, had a positive predictive accuracy of 96% and 93%, respectively, for the identification of a patent infarct artery. Therefore, sequential changes on tomographic 99mTc-sestamibi images are of potential value for the noninvasive assessment of patency of the infarct-related artery.