The cooperativity previously observed in the pH titration profiles of the histidine residues of rabbit tropomyosin was investigated. Nonpolymerizing tropomyosin was prepared by carboxypeptidase digestion and the titration profiles of its histidine residues were compared with those of undigested tropomyosin which was fully polymerized (in 0.1 M KCl) throughout the titration. Histidine-153 and histidine-273 apparently have significant cooperativity in their pH titrations only in polymerized tropomyosin. The cooperativity apparently arises from an intrinsic pH-dependent conformational transition which links the 2 residues together and not from the known pH dependence of the polymerization. The best model for the cooperativity may be a biallosteric adaption of the Monod-Wyman-Changeux formalism involving 2 classes of binding sites for the same ligand (protons). Three other models which postulated either a Hill transition, an interaction with a neighboring residue that titrates, or a pH-dependent polymerization were considered.