Measurements of vapor pressures over their aqueous solutions indicate that organic compounds show profound differences in hydrophilic character. These differences are of such magnitude as to suggest an important role for changing solvation in determining free energy changes associated with metabolic transformations in water, and in governing structural equilibria of proteins and other large molecules in water. When two or more functional groups are present within the same solute molecule, their combined effects on its free energy of solvation are commonly additive. Striking departures from additivity, observed in certain cases, indicate the existence of special interactions between different parts of a solute molecule and the water that surrounds it. Similar considerations presumably apply to activated intermediates in the interconversion of biological materials.