Kupffer cells (KC) represent the main part of the tissue macrophages. Beside phagocytosis of particulate material, involvement of KC in immunological and inflammatory reactions has been supposed. As C1 esterase inhibitor (C1-INH) is a serine protease inhibitor involved in such processes, the aim of this work was to study C1-INH synthesis in KC and, by comparison, in peritoneal macrophages (PM) and blood monocytes (MC) of the rat. C1-INH synthesis was studied on the protein level by biosynthetic labeling, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and on the RNA level by Northern blotting of total RNA or by in situ hybridization. KC were found to express C1-INH gene spontaneously. C1-INH synthesis represents 1.3 +/- 0.2% of total protein synthesis at day 1 of culture and the absolute amount each cell synthesis remains constant during the whole time in culture. Transcripts of C1-INH were detected both in freshly isolated and in cultured KC. In contrast, spontaneous C1-INH gene expression was not detectable in freshly isolated PM, but only in cultured PM. In MC, C1-INH was not detectable at any time, whatever. Treatment of the cells with interferon gamma increased C1-INH synthesis in KC and in PM and caused an induction of C1-INH synthesis in MC. The results suggest that constitutive C1-INH synthesis is a functional marker for mature tissue macrophages.