In this study we try to re-analyze thepH dependence of thermal stability of small globular proteins. From the thermodynamic point of view a long series of calorimetric
and spectroscopic investigations has shown that the decreased stability in very acidic conditions can be ascribed to entropic
effects. The same conclusion is reached, from a microscopic point of view, by assuming that a binding of protons on equal
and noninteracting sites takes place as a consequence of unfolding process. By linking the conformational unfolding equilibrium
to the proton binding equilibrium, a model is developed that is able to describe the dependence on thepH of the thermal denaturation processes of small globular protiens. The application of the model to hen lysozyme and T4 lysozyme
correctly accounts for the experimental results.