The proteolytic activity of the subtilisin Savinase is, with some substrates, radically enhanced at increased ionic strength. At some substrate positions the incorporation of more hydrophobic amino acid residues enhances the beneficial effects of salt addition. At other positions only the incorporation of charged amino acid residues leads to a significant change in the salt dependency. When the substrates are optimized with respect to hydrophobic interactions the enhancing effect of salt. declines. This demonstrates that the beneficial (rate enhancing) effects of salt addition cannot always be accounted for by simple models, e.g., the traditional "salting out" model.