We have previously reported that central injection of PGE₂ induces hyperthermia through its actions on EP₁ receptors in rats. Because the increase in local synthesis of PGE₂ is assumed to be a necessary process in a fever caused by central injection of interleukin-1 (IL-1), an EP₁ receptor antagonist (SC-19220) should inhibit the IL-1-induced fever. To test this hypothesis, we observed the effect of SC-19220 on the fever produced by injection of recombinant human IL-1 (rhIL-1) into the lateral cerebroventricle (LCV) in conscious rats. Administration of SC-19220 (100 µg) into the LCV 15 min before LCV injection of rhIL-1 (4 ng) suppressed an initial rise in colonic temperature for 30 min, producing a fever with a longer latency to onset and a longer time to peak elevation. SC-19220, given 60 min after the central administration of rhIL-1, also suppressed the rhIL-1-induced fever 15-60 min after its injection. These findings suggest that the central IL-1-induced fever in rats is mediated, at least partly, by activation of EP₁ receptors by PGE₂.