Hemopexin (Hpx) is a plasma glycoprotein which is expressed only in the liver. It is synthesized at a lower rate in the fetal liver than in the adult, and its level increases during acute infections. As shown here, a fragment of the human hemopexin promoter spanning from positions -130 to +22 relative to the cap site is sufficient to direct cell-specific transcription of a reporter gene. Within this segment a short sequence, located between positions -120 and -104, is responsible for this effect. This positive cis-acting element, the Hpx A site, interacts with a family of nuclear proteins, some of which are present only in hepatoma cells. The potential meaning of these complex DNA-protein interactions and the homology with elements present on the promoter of other liver-specific and acute phase genes are discussed.