Posttraumatic stress disorder (PTSD) is a serious mental illness which exhibits significant impairment of psychosocial and occupational function. At present, serotonin reuptake inhibitors (SRIs) show therapeutic promise for the treatment of PTSD. However, results in the veteran population have been less robust or often negative. In this study, a relatively new and the most selective SRI, citalopram, was evaluated for the treatment of PTSD. Veterans with chronic PTSD (N = 18) were enrolled in an 8-week open trial of citalopram after providing written informed consent. The primary outcome measures were the Clinician-Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Clinical Global Impression Scale (CGI). Seventeen patients completed at least 4 weeks of the 8-week trial. During treatment, there was a moderate response with 42% of patients demonstrating a > or =30% reduction in total CAPS score at week 8. Comparable results were demonstrated in the Hamilton Depression Rating Scale (HAM-D), HAM-A, Global Assessment of Function (GAF), and CGI rating scales. In a follow-up analysis, a treatment effect was shown for CAPS B at week 4, but was not sustained at week 8. Overall, citalopram was generally well tolerated with reported adverse events being benign in nature. These pilot results demonstrate a moderate effect of citalopram in the treatment of combat-induced PTSD. However, the sample size was small and patient population is limited to veterans with combat-induced PTSD. Further study in a larger and more diverse patient sample is warranted prior to final conclusions on efficacy of citalopram for the treatment of PTSD.