In this work we present studies of polymer-modulated permeation control (PMPC) where specific ligands and an inert polymer are covalently bound to a solid-phase adsorbent. The inert polymer serves mainly as obstacle for relatively large proteins. Thus only molecules of a size below a certain defined limit are able to penetrate onto the surface of the gel matrix. If these permeable molecules have strong chemical affinities for the gel-bound ligands, they will be retained. Other permeable solutes with no affinity will pass the bed with a weak retention due to the molecular sieving effects. Despite the many efforts to develop efficient protein purification techniques, the isolation of peptides and small proteins on a larger than analytical scale remains a significant challenge. In this work we present an approach that has the potential to obtain peptide separations of higher efficiency by combining molecular size effects and specific chemical affinities in rationally applied adsorption procedures. On the average, there are, fewer interaction sites per molecule in peptides than in proteins. If, therefore, ligand densities are increased for making peptide adsorption effective, protein adsorption is even more favored. This can be avoided by preventing proteins from entering gel phase regions where affinity ligands are located.