Interferon-alpha (IFN-alpha, 2.0 x 10(4) units) was bilaterally microinjected into the medial preoptic area and anterior hypothalamus in conscious rats treated 10 min prior with an opioid receptor antagonist, naloxone (NLX, 2 mg/kg, IM) or a prostaglandin synthetase inhibitor, acetaminophen (ACAP, 25 mg/kg, IM). The IFN-alpha-induced rise of rectal temperature (Tre) was suppressed from 20 to 60 min in NLX pretreated rats and from 30 to 180 min in ACAP pretreated rats. The rate of rise in Tre during the initial 20 min observed in NLX pretreated rats was significantly smaller than that in ACAP or saline pretreated rats. ACAP suppressed the fever when it was given 50 or 100 min after injection of IFN-alpha. In contrast, NLX did not affect the fever when given 25 or 50 min after IFN-alpha. The results suggest that an opioid that its involvement may last only in the early phase of the fever, but not after the plateau has been reached.