The redox potential of the Rieske iron-sulfur protein depends on pH. It has been proposed that the histidines coordinating one of the irons are responsible for this pH dependence, but an experimental proof for this proposal is still lacking. In this work, we present a density functional/continuum electrostatics calculation of the p K(a) values of the histidines in the Rieske iron-sulfur center. The calculated apparent p K(a) values are 6.9 and 8.8 in the oxidized state, which are in good agreement with the corresponding experimental values of 7.5 and 9.2 and the measured pH dependence of the redox potential. Neither of these two p K(a) values can, however, be assigned to only one of the histidines. We find that both histidines titrate over a wide pH range in the oxidized state. Reduction of the iron-sulfur center shifts the p K(a) values to 11.3 and 12.8, thus above 10.0 as found experimentally. The results provide a complete picture of the coupling of proton and electron binding, showing strongly cooperative binding of protons at electrode potentials near the redox midpoint potential of the cluster. The potential biological function of the low p K(a) value of the histidines and the shift upon reduction are briefly discussed.