We recently proposed a model of bradykinin bound to the rat bradykinin B2 receptor that is constructed on the basis of structural homology modeling to the criomicroscopic structure of the seven transmembrane domains of bacteriorhodopsin, extensive conformational searches and experimental mutagenesis results. On the basis of that model, a novel third-generation pseudopeptide antagonist, NPC 18325 (D-Arg1-Arg2-[aminotridecanoyl]3-Ser4-D-Tic5-Oic6++ +-Arg7) (Ki = 440 nM, guinea pig ileum), was designed and also reported. NPC 18325 has been proposed to adopt a C-terminal beta turn separated from N-terminal positive charges by a linear 12 carbon chain spacer. Experimentally, the four amino acids making up the C-terminus have been shown by NMR to preferentially adopt a beta turn at neutral pH in aqueous solution. We now present a series of peptides, related to and including NPC 18325, that explore the relationship between the length of the carbon chain and the affinity to the human bradykinin B2 receptor. The results show that there is a structure-activity relationship (SAR) associated with the chain length and that these pseudopeptides have better affinity to the human bradykinin receptor than they have to the guinea pig ileal-derived B2 receptor. Specifically, peptide I (a 12-methylene linker) had a measured Ki of 31 nM and peptide V (a 4-methylene linker) had a Ki of 471 nM. Implications regarding conformation and hydrophobicity are also described.