Depersonalization disorder is classified in DSM-III-R (APA 1987) as a dissociative disorder characterized by altered perception or experience of the self. To date, there are no known reports of the neurobiological features of this disorder. We report clinical and biological correlates in a patient with depersonalization disorder previously unresponsive to a variety of anticonvulsant, monoamine oxidase inhibitor, and tricyclic antidepressant trials, but for whom fluoxetine partially reduced depersonalization symptoms, but not associated anxiety and depression. Neurophysiological, neuroanatomical and neuropsychological findings revealed left hemispheric frontal-temporal activation and decreased left caudate perfusion. These findings suggest a similarity to the neuropsychiatric data reported in obsessive-compulsive disorder patients.