OBJECTIVE: In contrast to the recent surge of interest in other dissociative disorders, DSM-III-R depersonalization disorder has not been thoroughly investigated and characterized. The authors systematically elucidated its phenomenology, comorbidity, traumatic antecedents, and treatment history. METHOD: Thirty adult subjects (19 women and 11 men) were consecutively recruited and administered various structured and semistructured interviews as well as the self-rated Dissociative Experiences Scale. An age- and sex-matched normal comparison group was also recruited. RESULTS: The mean age at onset of depersonalization disorder was 16.1 years (SD = 5.2). The illness had a chronic course that was usually continuous but sometimes episodic. Severe distress and high levels of interpersonal impairment were characteristic. Unipolar mood and anxiety disorders were common, but none emerged as specifically related to the depersonalization. A wide variety of personality disorders was manifested; avoidant, borderline, and obsessive-compulsive were most common. Although not highly traumatized, the subjects with depersonalization disorder reported significantly more childhood trauma than the normal comparison subjects. Depersonalization had been typically treatment refractory; only serotonin reuptake inhibitors and, to a lesser extent, benzodiazepines had been of any therapeutic benefit. CONCLUSIONS: This study supports the conceptualization of depersonalization disorder as a distinct disorder with a characteristic course that is independent of mood, anxiety, and personality symptoms. A subtle relationship may exist between childhood trauma and depersonalization disorder that merits further investigation. The disorder appears to be highly treatment refractory, and prospective treatment trials are warranted.