This study examined the role of the interleukin-1 (IL-1) type I receptor (IL-1RtI) in the acute phase response (APR) to inflammation in mice. Turpentine (100 microliters/mouse) injected subcutaneously induced fever, lethargy, body weight loss, and anorexia in IL-1RtI wild-type mice. Knockout mice lacking the IL-1RtI were resistant to these effects of turpentine, supporting a role for this receptor in the APR to local inflammation. The intraperitoneal injection of a low (50 micrograms/kg) or high (2.5 mg/kg) dose of lipopolysaccharide (LPS) induced similar APRs in IL-1RtI wild-type and knockout mice. IL-1RtI knockout mice were resistant to the APR induced by peripherally injected murine IL-1 beta, suggesting that it is not the interaction of endogenous IL-1 beta with IL-1RtII that induces an APR to LPS in these mice. We speculate that the absence of IL-1RtI in these knockout mice results in the sensitization of other cytokine pathways to mediate the APR to LPS.