Arc and Mnt are homologous repressors which recognize operator sequences that differ at 8-10 important positions. Nevertheless, single residue changes in an Arc/Mnt hybrid protein can switch DNA-binding specificity between the two operators and even allow one particular hybrid to bind strongly to both operators. The ability of single residue changes to radically alter binding specificity involves: 'master' residues that mediate some base contacts directly and some base contacts indirectly through residue-residue hydrogen bonds; identical residues which can make alternative sets of DNA contacts in the two operators; and amplification of the effect of each mutation because the proteins bind operator DNA as tetramers.