Using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropyleneamine oxime (HM-PAO), we assessed brain perfusion in seven patients with panic disorder (PD) and in five age-matched normal subjects at rest. No patient had ever received drug treatment for panic. All patients were sensitive to lactate-induced panic. Computed tomography (CT) scans did not reveal any morphological abnormalities of the brain in any of the PD patients. Two indices of cerebral perfusion were calculated; these demonstrated alterations of brain perfusion in the PD group. Significant right-left asymmetry was found in the inferior frontal cortex of the PD patients. We also observed a significant blood flow increase in the left occipital cortex and a significant decrease in the hippocampal regions bilaterally. Although the changes seen in the inferior frontal cortex and occipital cortex may be related to anxiety experienced by the patients during the study, the pattern of hippocampal hypoperfusion appears to be characteristic of panic disorder. This suggests that the hippocampal structures may play an important role in the pathophysiology of panic disorder.