We investigated whether lipopolysaccharide (LPS)-induced hypothermia develops in a serotype-specific manner in biotelemetered conscious rats. Two different E. coli serotypes of LPSs were injected at a dose of 250 µg/kg, ip. E. coli O55:B5 LPS elicited an initial hypothermia and subsequent fever, but E. coli O111:B4 LPS caused more potent monophasic hypothermia. Serum tumor necrosis factor (TNF)- levels were dramatically elevated at the initial phase of the hypothermia induced by both LPSs. This elevation tended to subside at the nadir of E. coli O55:B5 LPS-induced response, but progressively increased at the nadir of E. coli O111:B4 LPS-hypothermia. Serum interleukin (IL)-10 levels were moderately elevated at the initial phase of the hypothermia and persisted at the same level at the nadir of each LPS-induced response. No change was observed at the serum IL-18 levels. A selective cyclooxygenase (COX)-1 enzyme inhibitor, valeryl salicylate (20 mg/kg, sc), abolished the hypothermia without any effect on the elevated cytokine levels. Another COX-1 selective inhibitor, SC-560 (1 mg/kg, sc) inhibited hypothermic responses as well. Meanwhile, cytokine levels were also reduced by SC-560 treatment. These findings suggest that LPS-induced hypothermia may have serotype-specific characteristics in rats. E. coli O111:B4 LPS has more potent hypothermic activity than E. coli O55:B5 LPS; that may presumably be related to its higher or sustained capability to release of antipyretic cytokines such as TNF-. COX-1 enzyme may be involved in for the generation of the hypothermia regardless of the LPS administered.