We have developed an algorithm for structure-based prediction of the effects of temperature on electrostatic interactions in proteins. This algorithm has been adapted for calculation of the pH dependence of the transition temperature (Tm) of proteins. The approach uses the G determined at one pH value by DSC as a reference point. The pH-dependent component of the free energy of stabilization of the native state is calculated from structure and used to "correct" the calorimetric G in order to account for the effects of pH on the stability of the protein. In order to test the algorithm, we have measured Tm vs pH for horse heart cytochrome-c over a range of conditions of ionic strength.