Early tomographic myocardial perfusion imaging with technetium-99m sestamibi was performed during inferior wall acute myocardial infarction to determine the relation between the amount and location of myocardium at risk and the presence or absence or anterior ST depression. The total size of the acute perfusion defect and its lateral and septal borders were measured in 29 consecutive patients who were admitted with > 30 minutes of chest pain and acute inferior ST elevation on their initial electrocardiogram. The 22 patients with anterior ST depression had significantly more left ventricular myocardium at risk than the 19 patients who did not have anterior ST depression (23 +/- 2% of the left ventricle vs 15 +/- 1%, p = 0.008). All 8 patients with > 25% of the left ventricle at risk had anterior ST depression. Patients with anterior ST depression had a significantly greater lateral extent of the acute perfusion defect (49 degrees +/- 8 degrees from the midinferior wall vs 23 degrees +/- 7 degrees, p = 0.002). There was no difference in the septal border of the perfusion defect between patients with and without anterior ST depression (-44 degrees +/- 4 degrees vs -46 degrees +/- 7 degrees, p = NS). No patient had a measurable anterior perfusion defect. Although there is considerable overlap between groups with and without anterior ST depression, anterior ST depression is a simple and readily available indicator of myocardium at risk in inferior wall acute myocardial infarction.