Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) induce nitric oxide synthase. The purpose of this study was to investigate the role of endogenous nitric oxide in IL-1beta-induced fever in rats. At a dose of 2.5 microg per animal intraperitoneal (i.p.) injections of rat recombinant IL-1beta evoked a febrile response with a duration of 8 hours. Simultaneous i.p. injection of 50 mg/kg N-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in a complete suppression of IL-1beta-induced fever in rats. I.p. injection of 50 mg/kg L-NAME alone had no apparent influence on body core temperature. Endogenous formation of IL-6 in response to IL-1beta was not suppressed but rather enhanced by treatment with L-NAME during the early stage of IL-1beta-induced fever. This result indicates that activation of nitric oxide synthase and thereby endogenous NO-formation is essential for the generation of an IL-1beta-induced febrile response in rats and that the suppression of IL-1beta-induced fever by treatment with L-NAME seems not to be caused by an inhibition of IL-6 production.