AbstractThis paper describes a theoretical work on the solubility of a protein in equilibrium between different forms such as isomerization (A ⇌ B) and dimerization (2A ⇌ B). Under the assumptions that A and B have different solubilities and form their own solid phases (in the form of either precipitation or crystal), it was shownthat only either A or B precipitates at a given condition, another form being in equilibrium in solution with the precipitating form, provided that the solubility ratio of A to B is not identical to their equilibrium composition in the solution phase determined by the equilibrium constant. It follows, then, that the total concentration of the protein in the solution phase can be calculated by summing the solubility of the precipitating form and the concentration in solution of another form in equilibrium with the precipitating form. Assuming various preferential protein‐solvent interactions for the two forms in solution as well as solid phases, dependences of the total protein solubility on the additive concentration were examined. It was shown that this dependence may be complex, showing maximum, minimum, or inflection point, depending on the preferential protein interactions with solvent components.