The finding that some opioid-mediated forms of stress-induced analgesia are antagonized by hypophysectomy and dexamethasone has led to the suggestion that beta-endorphin, released from the pituitary, may mediate these analgesic reactions. "Long-term analgesia" (an opioid-mediated form of stress-induced analgesia), which is blocked by dexamethasone and hypophysectomy, was also blocked by adrenalectomy and reinstated with corticosterone therapy. Corticosterone is proposed to play a permissive role in long-term analgesia and to be a critical hormone mediating this phenomenon.