AbstractTwo tris‐alkoxycarbonyl homoarginine derivatives, Boc‐Har{ω,ω′‐[Z(2Br)]2}‐OH and Boc‐Har{ω,ω′‐[Z(2Cl)]2}‐OH, were prepared by guanidinylation of Boc‐Lys‐OH, and used for the synthesis of neo‐endorphins and dynorphins. The results were compared with that obtained in the synthesis in which Boc‐Lys(Fmoc)‐OH was incorporated into the peptide chain, and after removing Fmoc protection, the resulting peptide‐resin was guanidinylated withN,N′‐[Z(2Br)]2‐ orN,N′‐[Z(2Cl)]2‐S‐methylisourea. The peptides were tested in the guinea‐pig ileum (GPI) and mouse vas deferens (MVD) assays. The results indicated that replacement of Arg by Har may be a good avenue for the design of biologically active peptides with increased resistance to degradation by trypsin‐like enzymes. Copyright © 20