Pax5 regulates the B cell-specific expression of the mb-1 gene together with members of the Ets family of transcriptional activators. The Ets proteins on their own bind poorly to the Pax5/Ets binding site, but can be recruited to the site by cooperative interactions with Pax5. The structure of the ETS domain of Ets-1 and the paired domain of Pax5 bound to DNA reveals the molecular details of the selective recruitment of different Ets proteins by Pax5. Comparison with structures of Ets-1 alone bound to both high- and low-affinity DNA sites reveals that Pax5 alters the Ets-1 contacts with DNA. The ability of one protein to alter the DNA sequence-specific contacts of another provides a general mechanism for combinatorial regulation of transcription.