We describe here a novel type of synthetic peptide library, named Multimeric Synthetic Peptide Combinatorial Library (M-SPCL), where multiple small peptide ligands are tied together in the same molecule. The advantage of using small peptides in the form of M-SPCL is two-fold: first, the high density assembly of the sequences on the branching scaffold leads to signal amplification, thereby effectively lowering the binding threshold for the selection of ligands; second, to interfere with protein-protein interactions, multimericity has been shown to be a desirable feature per se. The M-SPCL is prepared by solid-phase peptide synthesis, based on the structure of Multiple Antigen Peptides. When prepared in Positional Scanning format [C. Pinilla, J. Appel, P. Blanc and R.A. Houghten. 1992. BioTechniques 13: 901-905], selection is based on the amplified interaction of a single residue in a sequence-defined position. The usefulness of the new library was demonstrated by the selection of octameric peptides, which inhibit the binding of the cytokine human interleukin-6 to its receptor, with an apparent nanomolar affinity. Tetrameric, but not dimeric, branched peptides with the same sequences were also active with comparable affinity. The success of this approach is noteworthy, since screening of the corresponding monomeric pentapeptide SPCL did not lead to the selection of any inhibitory compound in the same system.