Protein C is a precursor of the anticoagulant serine protease, activated protein C, which inhibits coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C synthesis, we previously demonstrated that the kidney and male reproductive organs also expressed abundant protein C mRNA in the mouse. In the present study, we further investigated the effects of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and transforming growth factor-beta (TGF-beta) on the expression of protein C mRNA in the principal producing organs, i.e., the liver, kidney, and testis. Both quantitative reverse transcription-PCR assay and in situ hybridization analysis revealed that TNF-alpha decreased protein C mRNA expression in the liver, kidney, and testis. IL-1 also down-regulated protein C mRNA expression in the liver and testis, but not in the kidney. In contrast, TGF-beta unchanged the expression level of protein C mRNA in these three organs. These observations suggest that TNF-alpha and IL-1 may contribute to an increase in the procoagulant potential by downregulation of protein C synthesis in the tissues during inflammatory processes.