In cytochrome c oxidase, oxido-reductions of heme a/CuA and heme a3/CuB are cooperatively linked to proton transfer at acid/base groups in the enzyme. H+/e− cooperative linkage at Fea3/CuB is envisaged to be involved in proton pump mechanisms confined to the binuclear center. Models have also been proposed which involve a role in proton pumping of cooperative H+/e− linkage at heme a (and CuA). Observations will be presented on: (i) proton consumption in the reduction of molecular oxygen to H2O in soluble bovine heart cytochrome c oxidase; (ii) proton release/uptake associated with anaerobic oxidation/reduction of heme a/CuA and heme a3/CuB in the soluble oxidase; (iii) H+ release in the external phase (i.e. H+ pumping) associated with the oxidative (R→O transition), reductive (O→R transition) and a full catalytic cycle (R→O→R transition) of membrane-reconstituted cytochrome c oxidase. A model is presented in which cooperative H+/e− linkage at heme a/CuA and heme a3/CuB with acid/base clusters, C1 and C2 respectively, and protonmotive steps of the reduction of O2 to water are involved in proton pumping.