This study was designed to investigate the efficacy of the antidepressant drug bupropion in the treatment of posttraumatic stress disorder (PTSD). Seventeen male combat veterans with chronic PTSD were treated with bupropion in an open-label fashion for 6 weeks. Patients were evaluated with the Clinical Global Impressions Scale for Improvement (CGI-I) at follow-up and rated blindly at baseline and posttreatment with the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety. Three patients discontinued bupropion prematurely because of side effects. Of the remaining 14 patients, 10 were classified as treatment responders by the CGI-I. HAM-D scores decreased significantly from baseline to follow-up. The improvement seen in hyperarousal symptoms was significant but was less significant than the change in depressive symptoms. There was no significant change in Intrusion, Avoidance, or total CAPS scores. It was concluded that bupropion was well tolerated. Patients who had experienced sexual dysfunction with selective serotonin reuptake inhibitors reported no complaints during bupropion treatment. Bupropion decreased depressive symptoms and most patients reported global improvement, although PTSD symptoms remained mostly unchanged. Controlled trials should further clarify the role of bupropion in the treatment of PTSD.