This CT study was designed to assess brain morphology in panic disorder with and without agoraphobia. Twenty-one patients and 21 normal control subjects matched for age and sex were investigated. Frontal and parieto-occipital cortex, temporal cortex, lateral ventricles and 3rd ventricle were evaluated by qualitative assessment on a 3-point scale (normal, questionable, abnormal). Patients showed significant bilateral enlargement of cortical cerebrospinal fluid (CSF) spaces (p < 0.01). The rating "abnormal" was given to none (0%) of the normal controls, but to 7 (33.3%) of the patients. Explorative analysis showed that these abnormalities were predominantly located in prefrontal regions. No qualitative differences were seen in the temporal cortex, lateral ventricles or third ventricle. These findings support the hypothesis that alterations in brain morphology are involved in the etiology of panic disorder. The lack of a correlation between CSF enlargement and duration of illness suggests that frontal CSF enlargement is a neurobiological vulnerability marker in panic disorder.