Background: Much progress has been made in understanding the role of catecholamines in the pathophysiology of posttraumatic stress disorder (PTSD). Recent research has broadened the scope of neuroregulation of PTSD to include serotonin. Methods: We used the serotonin-releasing agent and reuptake inhibitor, d-fenfluramine, to assess the integrity of the serotonin- mediated prolactin release in 8 men with combat-induced PTSD and 8 healthy men. Results: The veterans with PTSD had a significantly lower prolactin response to d-fenfluramine as compared to healthy control subjects. The prolactin response to d-fenfluramine was inversely correlated with the patient's level of PTSD symptomatology and measures of aggression. Conclusions: This study demonstrates a central serotonin dysfunction, as reflected in a lower prolactin response to d-fenfluramine, in patients with PTSD.