A new approach regarding the solubility of various sparingly soluble solutes, such as proteins, drugs and gases, and the local structure around a solute molecule is presented. This approach is based on an expression for the activity coefficient derived through the Kirkwood-Buff fluctuation theory of solutions. First, an expression for the solubility of proteins in aqueous solutions in terms of the preferential binding parameter is derived and criteria for salting-out or salting-in by various cosolvents obtained. Second, the methodology developed for the solubility of proteins in water + cosolvent mixtures is extended to the solubility of sparingly soluble gases in the same kinds of solvents. The derived equation was successfully applied to the experimental data regarding the solubilities of oxygen, carbon dioxide and methane in water + sodium chloride. In addition, the excesses (or deficits) of water and sodium chloride molecules in the vicinity of a gas molecule have been calculated to conclude that the infinitely dilute solute gas molecules are preferentially hydrated. (c) 2007 Elsevier B.V. All rights reserved.