By using Western blot analysis, high levels of 17.5-and 20-kDa interleukin-1 (IL-1) proteins were detected in the submandibular gland (SMG) of mice. Despite this fact, the amount of pro-IL-1 protein, a precursor of IL-1, with a molecular size of 35 kDa in this tissue was below the detectable level, although strong expression of pro-IL-1 mRNA was observed. A large amount of 17.5-kDa IL-1 also appeared in the saliva of mice injected with lipopolysaccharide, suggesting that this IL-1 is a secretory form produced by the SMG. The protein for IL-1-converting enzyme, a processing enzyme for pro-IL-1, was expressed only at a low level in the SMG as compared with its level in various epithelial tissues or lipopolysaccharide-stimulated macrophages. On the other hand, mK1, mK9, mK13, and mK22, members of the kallikrein family, were detected strongly in the SMGbutnotinothertissues.ByincubationwithmK13,butnotwithmK1, mK9, or mK22, the 35-kDa pro-IL-1 was cleaved into two major products with molecular masses of 17.5 and 22 kDa, and production was inhibited by phenylmethylsulfonyl fluoride, a serine protease inhibitor, but not byIL-1-converting enzyme inhibitors. A peptide segment corresponding to amino acid residues 107-121 of mouse pro-IL-1 (