Background: In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective of the current study was to assess HPA-axis functioning in female adolescents with rape-related PTSD, but no prior sexual trauma, in comparison to non-victimized controls. Method: Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were measured in 52 female adolescent rape victims with PTSD and 37 healthy adolescents at 0, 15, 30, 45 and 60. min after awakening, both under basal conditions and after 0.5. mg dexamethasone administration. Results: Compared to age-matched controls, adolescent rape victims with PTSD showed significantly reduced cortisol and DHEAS levels. No group differences for the effect of dexamethasone suppression were found. Both the event of rape and PTSD diagnosis, and not factors such as sleep duration, smoking, education or oral contraceptives, accounted for the neuroendocrine differences between rape victims and controls. Conclusions: The results show evidence for a dysregulated HPA-axis in female adolescent victims of single sexual trauma with PTSD. The finding of hypocortisolism is consistent with endocrine dysfunctioning in chronic sexual abuse victims and may have clinical implications with regard to treatment possibilities. © 2012 Elsevier Ltd.