Sequence-directed recognition peptides (SDRPs) were constructed on the basis of their hydropathic complementarity for big-endothelin (bigET). These peptides can inhibit in vitro the proteolytic cleavage that generates endothelin (ET) from its bigET precursor. Comparison of dissociation constants of the complexes SDRP:bigET with kinetic constants obtained for the cleavage of bigET by alpha-chymotrypsin (taken as a model proteinase) provides evidence of the potential of SDRPs. This is a novel application of SDRPs used as inhibitors of a proteolytic reaction.