TRANSCRIPTION of the ant gene during lytic growth of bacteriophage P22 (ref. 1) is regulated by the cooperative binding of two Arc repressor dimers to a 21-base-pair operator site2,3. Here we report the co-crystal structure of this Arc tetramer-operator complex at 2.6 angstrom resolution. As expected from genetic4-6 and structural studies7 and from the co-crystal structure of the homologous Escherichia coli MetJ repressor8, each Arc dimer uses an antiparallel beta-sheet to recognize bases in the major groove. However, the Arc and MetJ complexes differ in several important ways : the beta-sheet-DNA interactions of Arc are far less symmetrical; DNA binding by Arc is accompanied by important conformational changes in the beta-sheet; and Arc uses a different part of its protein surface for dimer-dimer interactions.