Adjuvant-induced arthritis (AA) in the rat is a chronic inflammatory stress in which circulating corticosterone and interleukin (IL)-6 levels are elevated. In addition, there are profound neuroendocrine changes associated with the development of hind-paw inflammation which have major implications for the ability of the rat to respond to stress. Central injection of morphine is able to increase plasma corticosterone and circulating IL-6 concentration in control animals. In present study we have determined the effects of a single and repeated injection of morphine into the lateral ventricle of control and AA animals on plasma corticosterone, circulating IL-6 levels and course of hind-paw inflammation in AA rats. In the present study we found a sustained increase in plasma corticosterone both after single and repeated injection of morphine in control and AA rats and an increase of the level of circulating IL-6 in AA rats after repeated injection of morphine. These data suggest that alternative systems distinct from Athose activated in response to acute stress are activated by morphine in the AA animals. The similarity with the sustained increase in corticosterone following LPS injection suggest that central opiates may be involved in mediating HPA axis and cytokines response to inflammatory stress.