Transcriptional regulation and binding interactions between soluble nucleoproteins and the distal regulatory element (DRE) of the rat alpha 1-acid glycoprotein (alpha 1-AGP) gene were examined in the liver of rats during the acute-phase response. Our results show that the elevation of the alpha1-AGP gene transcription activity in acute phase liver relies basically on an increase in the binding-affinity of the constitutive soluble nucleoproteins with molecular masses 35 and 45 kD, enhancing their capability to bind to the distal regulatory element (DRE) of alpha-AGP gene. On the basis of in vitro phosphorylation/dephosphorylation experiments we discuss that the role of these proteins during alpha 1-AGP transcription may be dependent on their behavior as phosphoproteins. The 35kD nucleoprotein that displayed an acute-phase inducible affinity to bind DRE was identified as a C/EBP beta isoform.