Human C-reactive protein (CRP) is the major acute phase reactant during inflammation. Regulation of CRP gene expression has been studied in two experimental systems: transgenic mice and human hepatoma cells. In the first system the human CRP gene flanked by approximately 10(4) bases of 5' and 3' sequences is expressed in a liver-specific and inducible manner. The chromatin configuration of the CRP transgene is characterized by the presence of constitutive and inducible liver-specific DNase I-hypersensitive sites. Inducible sites map precisely at the level of the CRP promoter region. In hepatoma cells we analysed the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene driven by various segments of the CRP promoter. This latter approach has led to the identification of promoter elements responsive to interleukin-6 and of hepatocyte-specific nuclear proteins that interact with them.