The febrile responses induced by i.v. administrations of staphylococcal enterotoxin A (SEA) was mimicked by direct injection of SEA into the organum vasculosum laminae terminalis (OVLT) in unanesthetized rabbits. Compared with the febrile responses induced by i.v. injection of SEA, the OVLT route of injection required a much lower dose of SEA to produce a similar fever. Furthermore, the fever induced by intra-OVLT or i.v. injection of SEA was significantly attenuated by pretreatment with intra-OVLT injection of anisomycin (a protein synthesis inhibitor), indomethacin or diclofenac (inhibitors of cyclo-oxygenase (COX)), and aminoguanidine or dexamethasone (inhibitors of inducible nitric oxide synthase (iNOS)). These results suggest that COX or iNOS pathway in the OVLT mediate the SEA-induced fever in rabbits. (C) 1997 Elsevier Science Ireland Ltd.