Previous studies suggest that many transsexuals evidence an Axis I diagnosis according to the DSM-IV classification (e.g., psychoses, major affective disorder). The current study examined retrospectively the comorbidity between gender dysphoria and major psychopathology, evaluating the charts of 435 gender dysphoric individuals (318 male and 117 female). All had undergone an extensive evaluation, addressing such areas as hormonal/surgical treatment, and histories of substance abuse, mental illness, genital mutilation, and suicide attempts. In addition, a subgroup of 137 individuals completed the MMPI. Findings revealed over two thirds were undergoing hormone reassignment, suggesting a commitment to the real-life cross-gender process. One quarter had had problems with substance abuse prior to entering treatment, but less than 10% evidenced problems associated with mental illness, genital mutilation, or suicide attempts. Those completing the MMPI (93 female and 44 male) demonstrated profiles that were notably free of psychopathology (e.g., Axis I or Axis II criteria). The one scale where significant differences were observed was the Mf scale, and this held true only for the male-to-female group. Psychological profiles as measured by the MMPI were more "normal" in the desired sex than the anatomic sex. Results support the view that transsexualism is usually an isolated diagnosis and not part of any general psychopathological disorder.