Determination of defect size by sestamibi SPECT imaging five days post myocardial infarction has been considered to represent the final infarct size. This study prospectively examined serial sestamibi scans in 25 patients (age 54.5 +/- 11.1 y; 21 males) with first Q-wave myocardial infarction. Patients were treated with either thrombolysis (n = 5), primary PTCA/atherectomy/stents (n = 14), coronary artery bypass surgery (n = 2), or conventional therapy (n = 4). Coronary artery patency before the first sestamibi scan was documented in 23 pts. The initial sestamibi scan was performed at a median of 8 days post myocardial infarction (range 5-40 days, mean 10.5 days) with a median defect size of 36% of LV (range 0-76%). The second sestamibi scan post myocardial infarction (6 wks-6 mos) indicated a significant (p = 0.033) decrease in defect size to a median of 22% of LV (range 0-66%). Fourteen patients (56%) had a decrease of > 6%, the 95% confidence limit of reproducibility. No patient had a recurrent MI between scans. There was a weak correlation (r = 0.4; p = 0.07) between the decrease in defect size and the number of diseased vessels with stenoses > 70% luminal diameter. No correlation was found between the time to the first sestamibi scan and the change in defect size between the scans.Conclusion: 1) Patients with first Q-wave anterior MI receiving reperfusion therapy may have a significant reduction in sestamibi SPECT defect size between early (5-40 days) and late imaging (6 wks-6 mos). 2) Further studies will be needed to determine whether measurement of the defect size early or late post myocardial infarction has the most clinical relevance.