Macromolecular crowding affects many processes in the cell, where solvent mediated short and long range protein-protein electrostatic interactions, as well as protein-solvent interactions, occur at high protein concentrations in a complex mix of ionic species. The predominant view of macromolecular crowding considers only hard-sphere repulsions (solely entropic). However, as shown recently in the literature, the longer-range interactions can be stronger than the excluded volume effects. In this work, we quantify these interactions using isothermal titration calorimetry. We determined the interaction enthalpy between two proteins, lysozyme and human serum albumin, at high concentrations, at several pH values and, for one case, at three temperatures. We demonstrate that the long-range electrostatic interactions, attractive or repulsive, due to the charges on the protein surfaces dominate the interaction between them, and that the strength of these solvent-mediated forces can be tuned by changing the pH. (C) 2016 Elsevier B.V. All rights reserved.