This study examined the relationship between self-injurious behavior (SIB) in rhesus monkeys and several biological variables, including monoamine metabolites in cerebrospinal fluid (CSF) and circulating levels of ACTH, cortisol, and testosterone. Cisternal CSF and blood plasma samples were obtained from 23 individually housed male rhesus macaques, 14 of which had a veterinary record of self-inflicted wounding. CSF samples were analyzed for 5-hydroxyindole-3-acetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) using isocratic high-performance liquid chromatography with electrochemical detection (HPLC-EC). Plasma samples were analyzed for ACTH, cortisol, and testosterone using commercially available radioimmunoassays (RIAs). Rates of self-directed biting were determined by systematic observation of all monkeys. Monkeys with SIB did not differ from controls in their basal monoamine or gonadal activity. However, the SIB group showed consistently lower mean plasma cortisol levels than the control group. Plasma cortisol was negatively correlated with rates of self-directed biting. These results suggest a persistent dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in monkeys with SIB. It is not yet clear whether this phenomenon of low cortisol represents chronically reduced adrenocortical secretion under basal conditions or a difference in response to the mild stress of capture and chemical restraint. The implications of these findings will be discussed with respect to SIB in humans as well as post-traumatic stress disorder (PTSD), a condition characterized by pituitary-adrenocortical hypoactivity.