A method to screen combinatorial libraries for the development of selective ligands for protein affinity chromatographic purification is described. The method is based on the application of parallel combinatorial libraries, and it has several potential advantages. The screening procedure is simple and straightforward, and it does not require the chemical derivatization of the target proteins or even that the target protein be pure. The experiment can also be designed to select binders that are less likely to cause protein denaturation. Feasibility of this approach is demonstrated with a model study of the chromatographic purification of bovine albumin serum (BSA) and Avidin.