Several neuroanatomical hypotheses of panic disorder have been proposed focusing on the significant role of the amygdala and PAG-related "panic neurocircuitry." Although cognitive-behavioral therapy is effective in patients with panic disorder, its therapeutic mechanism of action in the brain remains unclear. The present study was performed to investigate regional brain glucose metabolic changes associated with successful completion of cognitive-behavioral therapy in panic disorder patients. The regional glucose utilization in patients with panic disorder was compared before and after cognitive-behavioral therapy using positron emission tomography with (18)F-fluorodeoxyglucose. In 11 of 12 patients who showed improvement after cognitive-behavioral therapy, decreased glucose utilization was detected in the right hippocampus, left anterior cingulate, left cerebellum, and pons, whereas increased glucose utilization was seen in the bilateral medial prefrontal cortices. Significant correlations were found between the percent change relative to the pretreatment value of glucose utilization in the left medial prefrontal cortex and those of anxiety and agoraphobia-related subscale of the Panic Disorder Severity Scale, and between that of the midbrain and that of the number of panic attacks during the 4 weeks before each scan in all 12 patients. The completion of successful cognitive-behavioral therapy involved not only reduction of the baseline hyperactivity in several brain areas but also adaptive metabolic changes of the bilateral medial prefrontal cortices in panic disorder patients.