Mouse fibroblasts in vitro secret kininogen (KGN). Rat fibroblasts also synthesized and secreted T-KGN in vitro. KGN production by these fibroblasts is greatly stimulated by dibutyryl cAMP, prostaglandin E2 and tumor necrosis factor. Human fibroblast WI-38 cells also express the L-KGN gene, which was stimulated by dibutyryl cAMP and prostaglandin E2. These results demonstrate that fibroblasts express the KGN gene, and suggest that the expression is regulated by inflammatory mediators. RT-PCR, using specific primers for the T-KGN and L-KGN genes, reveals that the rat hind-paw express both T- and L-KGN mRNAs, and the expression of both KGN mRNAs was increased in the hind-paw 24 h after inducing inflammation by injecting Freund's complete adjuvant into the paw. Thus, it is suggested that local connective tissues express the KGN gene, and that the expression is enhanced under pathological conditions, such as inflammation.