Background: Domestic violence (DV) is a major health problem. To date, the “fight” behavior manifested by perpetrators of domestic violence (PDV) has largely been attributed to psychosocial causes, with little emphasis given to biological antecedents. Since cytokines can modulate brain processing and have been associated with human aggression, we postulated that changes in cytokine levels may have a role in the pathology of DV. Methods: We obtained cerebral spinal fluid (CSF) as well as plasma samples from PVD with and without a diagnosis of alcohol dependence, as well as alcoholics and healthy controls without a history of DV. The presence or absence of violence as well as a lifetime diagnosis of PTSD were analyzed as independent variables and alcohol dependence was a covariate. Findings: Patients with a history of DV had significantly higher CSF concentrations of IL-6 and IL-8 than the non-violent controls. The IL-6 effect was driven by an interaction of perpetrator status and a lifetime diagnosis of PTSD. There were no correlations between the cytokine levels present in the CSF and those in the plasma. Interpretation: Our results, add to a growing literature indicating that cytokines have a role in psychopathology. The interaction between IL-6 and PTSD suggests that trauma may alter the production of cytokines, and thereby modulate the neuropathways that facilitate fight behavior. Fight behavior conveys survival benefit in war but becomes pathological in the home-setting with devastating consequences. Funding Statement: This research was supported by the Intramural NIAAA research program. Declaration of Interests: All authors report no biomedical financial interests or potential conflicts of interest. Ethics Approval Statement: This study was approved by the NIH Institutional Review Board. All participants provided written informed consent before participation.