The reactions of hemoglobin with various ligands lead to conformational changes in the macromolecule. The free energy of these changes can be estimated in terms of the surface free energy of a microemulsion droplet of the same size and surface charge as the hemoglobin molecule. Calculations on the basis of this model yield an equilibrium constant that varies with pH, as in the acid and alkaline Bohr effects, and with the ionic strength. The model also provides a physical meaning for the empirical constant in the oxygen binding equation, as well as some insight into the dissociation equilibrium of the hemoglobin tetramers. This approach to equilibria involving globular proteins should be useful for estimating the effects of conformational changes and subunit interactions in other systems.