HUMAN T-cell leukaemia virus type I(HTLV-I) Tax protein increases the DNA binding of many cellular transcription factors that contain a basic region-leucine zipper (bZIP) DNA-binding domain(1-3). bZIP domains comprise a leucine-rich dimerization motif and a basic region that mediates DNA contact. How Tax recognizes diverse bZIPs is not understood. Here we show that no specific sequence of the leucine zipper is required for a Tax response. In contrast, the basic region is essential for the Tax-mediated DNA-binding increase, which can be eliminated by single substitutions of several conserved amino acids. Surprisingly, Tax alters the relative affinity of a bZIP for different DNA binding sites. Thus, through recognition of the conserved basic region, Tax increases DNA binding and modifies DNA site selection. Tax provides a model for how a single auxiliary factor can regulate multiple sequence-specific DNA-binding proteins.