A thermodynamic model is presented to describe the redox behaviour of the tetraheme cytochrome c3 from Desulfovibrio gigas. This molecule displays different intrinsic redox potentials for the four hemes and during the redox titration process, interactions among different hemes occur, thus altering the values of redox potentials according to which of the hemes are oxidized [Santos, H., Moura, J.J.G., Moura, I., LeGall, J. & Xavier, A.V. (1984) Eur. J. Biochem. 141, 283-296]. This complex cooperative behaviour [Xavier, A.V. (1986) J. Inorg. Biochem. 28, 239-243] has been analyzed here using an I2H4-interaction network [Cornish-Bowden, A. & Koshland, D.E. Jr (1970) J. Biol. Chem. 245, 6241-6250] coupled to a proton-linked equilibrium between two tertiary structures. Such a formalism, which requires a reduced number of parameters, is able to fully account quantitatively for the pH dependence of the NMR redox-titration curves. The 'redox-Bohr' effect is discussed in terms of the available structure and thermodynamic data and a functional mechanism is proposed.