The primary determinant of prognosis after acute myocardial infarction (AMI) is the size of the acute infarct. The present study evaluates 46 patients with different infarct distributions and sizes to test the hypothesis that single photon emission computed tomography with technetium-99m pyrophosphate (Tc-99m-PPi) and blood pool overlay allows measurements of AMI size that provide insight into prognosis irrespective of infarct location. Identical Tc-99m-PPi and ungated blood pool projections were acquired over 180 degrees with a rotating gamma camera. Reconstructed sections were color-coded and superimposed for purposes of infarct localization. Areas of increased pyrophosphate uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted so as to determine an endocardial border for the left ventricle. Using this method, myocardial infarcts weighed 2.5 to 81.2 g. The correlation of infarct mass with prognosis showed that patients without previous AMI and with acute infarcts that weighed more than 40 g had an increased frequency of death and congestive heart failure (p less than 0.001). The correlation of measured infarct mass with peak serum creatine kinase level was significant (r = 0.83, p less than 0.001; y = 0.015x + 13.20). The correlation coefficients for anterior, inferior and nontransmural AMI were not significantly different from those for the entire group. In conclusion, tomographically determined infarct mass data correlate with subsequent clinical prognosis, and Tc-99m-PPi tomography with blood pool overlay is a safe and effective means of sizing infarcts in patients with AMI.