Mice subjected to defeat in a social conflict paradigm display an analgesic response that is apparently mediated by endogenous opioids. It is blocked by naloxone and shows full cross-tolerance to and from morphine. The present study investigated the contribution of sources of endogenous opioids outside of the central nervous system, namely the pituitary and adrenal glands. Treatment known to enhance (metyrapone pretreatment), reduce (2% saline in the drinking water) or block (dexamethasone pretreatment) the release of beta-endorphin from the anterior pituitary did not affect the display of analgesia in defeated mice. Similarly, treatments known to enhance (reserpine pretreatment) or block release of enkephalins (removal of the adrenals or hexamethonium pretreatment) from the adrenal medulla also failed to influence defeat-induced analgesia in the expected manner. If anything, adrenalectomy enhanced and reserpine pretreatment suppressed the analgesic response to defeat. The data are discussed in terms of providing evidence that defeat-induced analgesia is mediated primarily by endogenous opioids released and acting within the central nervous system.