Background. We obtained pilot data to examine the clinical and neuroendocrine effects of short-term mifepristone treatment in male veterans with PTSD.Methods. Eight male veterans with military-related PTSD completed a randomized, double-blind trial of one week of treatment with mifepristone (600 mg/day) or placebo. The primary clinical outcome measures were improvement in PTSD symptoms and dichotomously defined clinical responder status as measured by the CAPS at one-month follow-up. Additional outcome measures included self-reported measures of PTSD symptom severity, CAPS-2 symptom subscale scores, and morning plasma cortisol and ACTH levels.Results. Mifepristone was associated with significant improvements in total CAPS-2 score. At one-month follow-up, all four veterans in the mifepristone group and one of four veterans in the placebo group achieved clinical response; three of four veterans in the mifepristone group and one of four veterans in the mifepristone group remitted. Mifepristone treatment was associated with acute increases in cortisol and ACTH levels and decreases in cytosolic glucocorticoid receptor number in lymphocytes.Conclusions. Further controlled trials of the effects of mifepristone and their durability are indicated in PTSD. If effective, a short-term pharmacological treatment in PTSD could have myriad uses.