In performing displacement chromatography for the purification of biomolecules, one of the biggest challenges has been the selection of the proper high affinity displacer. The displacer not only has to have sufficient dynamic affinity to carry out the displacement but must also have suitable operational properties which will enable a cost effective and simple process. One of these requirements is the non-toxic nature of the displacer, which if satisfied will make displacement chromatography a more attractive tool for biopharmaceutical applications. In this study, a new non-toxic low molecular weight displacer, saccharin, was introduced and characterized for the purification of an oligonucleotide and proteins by anion exchange displacement chromatography. It was demonstrated that saccharin, with only one charge, can indeed displace and purify very highly retained oligonucleotides and proteins. The operating conditions for the displacement experiments were predicted using operating regime plots. The results indicate that saccharin is not only effective as a displacer for isotachic displacements but for selective displacements as well. (C) 2002 Elsevier Science B.V. All rights reserved.