It has been hypothesized that endogenous glucocorticoids represent an important negative feedback system involved in the modulation of cytokine-induced fever through the inhibition of prostaglandins (PG) production in the preoptic anterior hypothalamus (AH/POA). The purpose of this study was to determinate whether glucocorticoids modulate the PG-independent febrile response induced by macrophage inflammatory protein-1beta (MIP-1beta) in a manner similar to other pyrogenic cytokines. Subcutaneous pretreatment with dexamethasone (1, 2 and 4 mg/kg; 1 h) had no effect on fever induced by microinjection of 50 pg MIP-1beta into the rat's AH/POA. It is demonstrated for the first time that, unlike other cytokines, fever induced by MIP-1beta is independent of glucocorticoid modulation. Finally, these results offer new perspectives about the pathogenesis of glucocorticoid-unresponsive pyrexia.