When a protein binds a ligand, hydrogen ions may be liberated or consumed. When this occurs, the apparent equilibrium constant K' for the dissociation of the ligand will be a function of pH. Thus, the study of the dependence of K' on pH can provide information on the acid dissociation constants of acid groups in the binding site of the protein before and after binding a ligand. From a thermodynamic point of view, the acid titration curves of the protein, ligand, and protein-ligand complex are related to the pH dependence of K' through the hydrogen ion binding polynomials P (partition functions) of the three reactants. However, the hydrogen ion binding polynomials of the protein and protein-ligand complex can be factored into a binding polynomial for the site and a binding polynomial for the rest of the protein molecule. When the ligand does not have acid dissociations in the range of pH where the unoccupied site or occupied site does, the pH dependence of K' is given by the ratio of the binding polynomial of the unoccupied site to the binding polynomial of the occupied site. When there are two acid groups in the site, it is shown that all four acid dissociation constants can be calculated from the dependence of IT on pH, even if there is positive cooperativity in the binding site. The pH dependencies of the standard transformed Gibbs energy of formation of the catalytic site in fumarase and for the site occupied by succinate and the three isomers of tartrate are calculated.