Purpose: Although several neuroanatomical models of panic disorder have been proposed, little is known regarding the neurological mechanisms underlying cognitive-behavioral therapy (CBT) in patients with panic disorder. This study was performed to identify the brain structures that show changes of regnioal cerebral blood flow (rCBF) after CBT in patients with panic disorder. Materials and Methods: Seven patients who were diagnosed as panic disorder by DSM-IV were treated with CBT for 8 weeks and twelve healthy volunteers joined in this study. Serial ^99mTc-ECD brain perfusion SPECT images were acquisited and PDSS-SR (Self-Report version of Panic Disorder Severity Scale) and ACQ (Agoraphobic Cognitive Question) scores were measured just before and after CBT in all patients. Data were analyzed using SPM2. Results: Subjective symptoms were improved, and PDSS-SR and ACQ scores were significantly reduced (14.9¡¾3.9 vs. 7.0¡¾1.8, p<0.05; 30.3¡¾8.5 vs. 21.6¡¾3.4, p<0.05, respectively) after CBT in panic patients. Before CBT, a significant increase of rCBF was found in the cingulate gylus, thalamus, midbrain, both medial frontal and temporal lobes of the panic patients compared to the normal volunteers. After CBT, we observed a significant rCBF decrease in the left parahippocamus, right insula and cingulate gyrus, both frontal and temporal lobes, and a significant rCBF increase in both the occipital lobes, left insula, both frontal and left parietal lobes. Conclusion: These data suggested that CBT is effective for panic disorder and diminish the activity of the brain areas associated with fear in panic disorder. (Nucl Med Mol Imaging 2006;40(6):302-308)