99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-Sestamibi), a new myocardial perfusion radiopharmaceutical, was injected intravenously in 11 patients within 4 hours of the onset of acute myocardial infarction before treatment with intravenous tissue-type plasminogen activator and 6-14 days later. Five patients with acute myocardial infarction who did not receive intravenous thrombolytic therapy underwent a similar injection of radiopharmaceutical. The absence of redistribution of Tc-Sestamibi permitted imaging with single-photon emission computed tomography up to 6 hours after intravenous injection to assess the distribution of myocardial perfusion at the time of administration. The region of hypoperfused myocardium on the initial images varied widely from 9% to 68% of the left ventricle and was significantly greater in anterior than in inferior infarcts (p less than 0.01). The region of hypoperfused myocardium on the final images varied widely from 0% to 63% of the left ventricle and was also greater in anterior infarcts (p less than 0.01). The final hypoperfused region correlated (r = -0.82) with the late resting ejection fraction and with the late regional wall motion score in the infarct segment for both anterior (r = -0.74) and inferior (r = -0.97) infarcts. There was a significant decrease (-13 +/- 11%, p less than 0.003) in the extent of hypoperfused myocardium between the initial and final studies in the patients who received thrombolytic therapy compared with an insignificant increase (4 +/- 6%, p greater than 0.5) in the patients who did not receive thrombolytic therapy. Tomographic imaging with Tc-Sestamibi permits determination of the amount of hypoperfused myocardium "at risk" in acute myocardial infarction. The change in myocardial perfusion determined by Tc-Sestamibi before and after therapy in acute myocardial infarction is a promising tool for assessing treatment.