Depersonalization and derealization are commonly reported in the general population as a response to stress. The symptoms have also been described in patients with a primary psychiatric or organic diagnosis, where their secondary status precludes a DSM-IV diagnosis of depersonalization disorder. The authors present 4 new cases of depersonalization in patients with an underlying organic condition, along with 47 cases from the literature in which the available information permits diagnosis of organic depersonalization. Information from case series documenting depersonalization in the context of medical illnesses is also presented and the underlying etiology discussed. Epilepsy and migraine appear to be the disorders most commonly associated with depersonalization. Left-sided temporal lobe dysfunction and anxiety are suggested as factors in the development of depersonalization; however, further studies are needed to determine the relationship. The introduction to the DSM-IV of an organic subtype of depersonalization disorder would facilitate research in this area.