Interleukin 6 (IL-6) is responsible for a variety of biological effects related to the activation of defenses against infection or inflammation, including the immune response and the acute-phase reaction. Its mechanism of action is unknown. It has recently been shown to induce transcription of several genes encoding acute-phase proteins. Here we describe the identification of an IL-6 responsive element (IL-6RE) present in the promoter of the human hemopexin gene. This element is necessary and sufficient for the IL-6-dependent activation of transcription. The IL-6 effect does not require de novo protein synthesis. A liver-specific nuclear protein (IL-6DBP) binds to the hemopexin IL-6RE as well as to similar sequences on the promoter of other acute-phase genes. IL-6DBP DNA binding activity is induced by IL-6 via a posttranslational mechanism.