Panic disorder is characterized by recurrent anxiety attacks in the absence of a frightening stimulus. It is a common disorder, affecting 2-5% of the general population and 10-14% of patients seen in cardiology practice. Infusion of sodium (DL)lactate precipitates an anxiety attack in most persons with this disorder but rarely does so in normal controls, suggesting a neurobiological basis for the problem. Despite this observation, the pathophysiology of panic disorder remains unknown. We have now used positron emission tomography to measure cerebral blood flow (CBF) in patients with panic disorder in the absence of a panic attack. Analysis of CBF in regions thought to mediate symptoms of panic, anxiety and vigilance reveals a significant (P less than 0.005) abnormal asymmetry of CBF (left less than right) located in a region of the parahippocampal gyrus. This asymmetry was present in seven patients with panic disorder and a positive response to lactate infusion but was absent in six normal controls and in three patients with panic disorder associated with a negative response to lactate. We believe this to be the first study to identify a discrete brain abnormality in patients with this severe form of anxiety.