Silica immobilized bovine serum albumin (BSA) has been synthesized and studied chromatographically using D, L-tryptophan and L-Kynurenine. Site specific and background interactions have been measured as a function of temperature and treatment with methanol. The results indicate that solvent entrapment in the interior hydrophobic region of the protein may lead to small changes in conformation and/or dynamics which influence the site specific binding of the protein and hence changes in chromatographic retention. The entrapped solvents appear to be thermodynamically and kinetically stable such that their influence on the protein persists at elevated temperatures and over hundreds of column volumes of aqueous buffer eluent.