In this work, osmotic second virial coefficients (B22) were determined and correlated with the measured solubilities for the proteins, a-amylase, ovalbumin, and lysozyme. The B22 values and solubilities were determined in similar solution conditions using two salts, sodium chloride and ammonium sulfate in an acidic pH range. An overall decrease in the solubility of the proteins (salting out) was observed at high concentrations of ammonium sulfate and sodium chloride solutions. However, for a-amylase, salting-in behavior was also observed in low concentration sodium chloride solutions. In ammonium sulfate solutions, the B22 are small and close to zero below 2.4 M. As the ammonium sulfate concentrations were further increased, B22 values decreased for all systems studied. The effect of sodium chloride on B22 varies with concentration, solution pH, and the type of protein studied. Theoretical models show a reasonable fit to the experimental derived data of B22 and solubility. B22 is also directly proportional to the logarithm of the solubility values for individual proteins in salt solutions, so the log-linear empirical models developed in this work can also be used to rapidly predict solubility and B22 values for given proteinsalt systems. (c) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012