Background: Patients with chronic psychiatric diagnoses have a prevalence of chronic hepatitis C (HCV) approximately 11 times higher than the general American population. Posttraumatic stress disorder (PTSD) is particularly common among HCV patients. Objective: The authors describe the effect of treatment with pegylated-interferon-α2b (IFN) and ribavirin for patients with HCV on their posttraumatic stress disorder (PTSD) symptoms. Method: Sixteen patients with HCV and combat-related PTSD were followed for 24 weeks and assessed with self-report measures of PTSD, hostility, and depression. Results: Depression and Resentment scores significantly increased in five patients treated with IFN and ribavirin, but no significant differences were found in PTSD scores when compared with 11 control patients. Conclusion: The results suggest that patients with PTSD and HCV can be safely treated with anti-viral therapies when they are given appropriate psychiatric care.