Subchronic (36 h) exposure of rats to corticosterone (CS) (100 mg/pellet, subcutaneously), blocked the pyrogenic response to recombinant human interleukin 1b (rhIL-1b, 5 mg/kg, ip.). CS treatment reduced the basal mRNA levels of IL-1a and IL-1b, but elevated the mRNA levels of IL-6 in the hypothalamus and hippocampus as shown by RT-PCR. The CS treatment clamped the cytokine mRNA levels, and injection of rhIL-1b to CS treated rats did not significantly affect these altered mRNA levels. IL-6 bioactivity in serum was not significantly changed by CS treatment, but increased 50 times upon injection of rhIL-1b. rhIL-1b caused a significantly lower induction of serum IL-6 levels in CS pretreated rats (9-fold). The pyrogenic response to injection of rhIL-1b has returned 5 days after the removal of the corticosterone pellet, and the hypothalamic cytokine mRNA levels (IL-1a, IL-1b and IL-6) have returned to basal. These results suggest that altered and clamped hypothalamic IL-1a, IL-1b and IL-6 mRNA levels may be involved in the antipyretic effects of a pretreatment with high doses of CS and that these CS effects are rapidly reversible.