Purpose: To assess the effect of extracranial-intracranial (EC-IC) bypass surgery on hemodynamic improvement, we evaluated serial regional cerebral hemodynamic change of the middle cerebral artery (MCA) in symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or MCA using 99mTc-ECD acetazolamide stress brain perfusion SPECT (Acetazolamide SPECT). Materials and Methods: The patients who had suffered a recent stroke with atherosclerotic ICA or MCA occlusion underwent EC-IC bypass surgery and Acetazolamide SPECT at 1 week before and three to six months after surgery. For image analysis, attenuation corrected images were spatially normalized to SPECT templates with SPM2. Anatomical automated labeling was applied to calculate mean counts of each Volume-Of-Interest (VOI). Seven VOIs of bilateral frontal, parietal, temporal regions of the MCA territory and the ipsilateral cerebellum were defined. Using mean counts of 7 VOIs, cerebral perfusion index and perfusion reserve index were calculated. Results: Seventeen patients (M:F=12:5, mean age: 53¡¾2yr) were finally included in the analysis. The cerebral blood flow of the parietal region increased at 1 week (p=0.003) and decreased to the preoperative level at 3-6 months (p=0.003). The cerebrovascular reserve of the frontal and parietal regions increased significantly at 1 week after surgery (p<0.01) and improved further at 3-6 months. Conclusion: Cerebrovascular reserve of the MCA territory was significantly improved at early postoperative period after EC-IC bypass and kept improved state during long-term follow-up, although cerebral blood flow did not significantly improved. Therefore, cerebrovascular reserve may be a good indicator of postoperative hemodynamic improvement resulted from bypass effect. (Nucl Med Mol Imaging 2008;42(1):8-16)