BACKGROUND Neurochemical studies have pointed to a modulatory role in human aggression for a number of central neurotransmitters; some (e.g., serotonin) appear to play an inhibitory role, while others (e.g., vasopressin) appear to play a facilitator role in the modulation of aggression. While recent animal studies of neuropeptide Y (NPY) have suggested a facilitator role for central NPY in the modulation of aggression, no human studies of central NPY have yet been reported regarding aggression. METHODS Basal lumbar cerebrospinal fluid (CSF) was obtained from 60 physically healthy subjects with personality disorder (PD) (n=40) and from healthy volunteers (n=20). These samples were then assessed for CSF NPY-like immunoreactivity (NPY-LI) and other neurotransmitter-related species in CSF and correlated with measures of aggression and impulsivity. RESULTS Cerebrospinal fluid NPY-LI was higher in PD subjects compared with healthy volunteers and in subjects with intermittent explosive disorder compared with those without intermittent explosive disorder. In PD subjects, CSF NPY-LI was directly correlated with composite measures of aggression and impulsivity and a composite measure of impulsive aggression. Group differences in CSF NPY-LI concentration were accounted for by measures of impulsive aggression. CONCLUSIONS These data suggest a direct relationship between CSF NPY-immunoreactivity concentration and measures of impulsive aggression in human subjects. This adds to the complex picture of the central neuromodulatory role of impulsive aggression in human subjects.