IL-β is an endogenous pyrogen that is inducedduring systemic lipopolysaccharide (LPS)- or IL-1-induced fever. We have examined the fever and cytokineresponses following i.p. injection of IL-1 agonists, IL-1a andIL-β, and compared these with response to LPS (i.p.) in wild-type and IL-β-deficient mice. The IL-β deficient mice appear to have elevated body temperature but exhibit a normal circadian temperature cycle. Exogenously injected IL-β, IL-1a, or LPS induced hyperresponsive fevers in the IL-βdeficient mice. We also observed phenotypic differences between wild-type and IL-β-deficient mice in hypothalamic basal mRNA levels for IL-1a and IL-6, but not for IL-βconverting enzyme or IL-1 receptor type I or type II. The IL-1a mRNA levels were down-regulated, whereas the IL-6 mRNA levels were up-regulated in the hypothalamus of IL-βdeficient mice as compared with wild-type mice. The IL-βdeficient mice also responded to LPS challenge with significantly higher serum corticosterone and with lower serum tumor necrosis factor type a levels than the wild-type mice. The data suggest that, in the redundant cascade of proinflammatory cytokines, IL-β plays an important but not obligatory role in fever induction by LPS or IL-1a, as well as in the induction of serum tumor necrosis factor type a and corticosterone responses either by LPS or by IL-1a or IL-β.