Experiments on anesthetized male rats were performed to study the role of the hormones of the hypothalamo-hypophyseal-adrenocortical system (HHACS) in analgesia induced by central or systemic administration of corticoliberin-releasing hormone (CRF). Studies of the contribution of HHACS hormones were performed by blocking HHACS function by administration of hydrocortisone at a pharmacological dose one week before experiments started. Blockade of HHACS function, resulting in the inability of the system to increase hormone levels, resulted in a decrease in the analgesic effect resulting from systemic administration of CRF and completely abolished the analgesic effect after central administration of CRF. These data lead to the conclusion that there are two components involved in increasing the pain sensitivity threshold in response to administration of CRF: 1) a component dependent on HHACS hormones in central and systemic administration of CRF; 2) a component independent of HHACS hormones on systemic administration of CRF.