When injected intravenously into humans and animals, interleukin‐1β (IL‐1β) is perhaps the most potent of the endogenous pyrogens. However, IL‐1β is initially synthesized as a relatively inactive precursor molecule (proIL‐1β) which lacks a signal peptide and hence remains inside the cell. To be active as a fever‐producing molecule, proIL‐1β must first be processed to an active mature molecule and secreted. Although several enzymes associated with inflammatory tissues are capable of processing proIL‐1β into an active molecule in the extracellular compartment, the IL‐1β converting enzyme (ICE, also called caspase‐1) cuts intracellular proIL‐1β after the aspartic acid residue in position 116, resulting in a highly active mature IL‐1β that is secreted into the extracellular space. IL‐18 is also initially synthesized as an inactive precursor molecule (proIL‐18) lacking a signal peptide. IL‐18 is a member of the IL‐1 family, and like IL‐1β, proIL‐18 is cleaved by ICE to yield an active molecule. However, unlike IL‐1β, IL‐18 is not an endogenous pyrogen following intraperitoneal injection into mice. Nevertheless, IL‐18 may contribute to inflammation and fever because IL‐18 is a potent inducer of tumor necrosis factor, chemokines, and interferon‐γ production.