The roles of interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF) in lipopolysaccharide (LPS)-induced fever were investigated in the rat. We used antisera against IL-1 beta and TNF to determine whether we could alter the fever by blocking the action of these cytokines. The intravenous injection of antiserum IL-1 beta 3.5 days before the intraperitoneal injection of LPS resulted in a mean fever that was significantly lower than that seen in rats that had been injected with control serum (0.36 +/- 0.11 vs. 0.82 +/- 0.16 degrees C, P = 0.016). The intravenous injection of antiserum against TNF 3.5 days before the intraperitoneal injection of LPS did not block the fever but significantly enhanced it (1.31 +/- 0.16 vs. 0.82 +/- 0.16 degrees C, P = 0.027). These data support the hypotheses that IL-1 beta is responsible for a significant part of LPS fever and that TNF acts as an endogenous antipyretic to limit the magnitude of LPS fever in the rat.