A new formulation (SPACE) is presented for the prediction of infinite dilution activity coefficients in nonionic solutions. Statistical methods have been used to develop a critically evaluated γ∞ database at 25 °C and to determine optimum mathematical expressions. The predictive method stems from earlier work using additive contributions to the cohesive energy density, but all compound-specific adjustable parameters have been avoided by using known molecular properties, especially the solvatochromic parameters for dipolarity/polarizability and for hydrogen bonding. This method has the advantages of including explicitly “chemical” interactions and of being uncoupled from any specific gE(x) expression. For the present, it is limited to monofunctional molecules at 25 °C, and it has not yet been applied to water. Although it appears somewhat more accurate for this database than the UNIFAC method, it should be viewed as a complementary technique—an additional tool for solvent selection by the design engineer.