The effect of opiate agonists and antagonists on the induction of serum interleukin-6 (IL-6), an inflammatory cytokine that plays a major role in the acute phase response, was studied. Morphine (10 micrograms, i.c.v. or 15 mg kg-1, i.p.), beta-endorphin (0.5 or 5 micrograms, i.c.v.) and etorphin (10 mg kg-1, i.p.) induced IL-6. Moreover, morphine potentiated the IL-6 response induced by IL-1 beta (400 ng, i.p. or i.c.v.). When injected intraperitoneally, the opiate antagonist naloxone hydrochloride, antagonized the IL-6 response induced by either i.c.v. or i.p. IL-1 beta. This effect was not seen with naloxone methiodide, which does not cross the blood-brain barrier. The data show that central opiates are effective modulators of the inflammatory cytokine IL-6.