Structural　homologues　of　vertebrate　regulatory　peptides　found　in　defensive　skin　secretions　of　anuran　amphibians　often　display　enhanced　bioactivity　and　receptor　binding　when　compared　with　endogenous　mammalian　peptide　ligands.　Maximakinin,　a　novel　N-terminally　extended　bradykinin　(DLPKINRKGPRPPGFSPFR)　from　the　skin　venom　of　a　Chinese　toad　(Bombina　maxima),　displays　such　activity　enhancement　when　compared　with　bradykinin　but　is　additionally　highly　selective　for　mammalian　arterial　smooth　muscle　bradykinin　receptors　displaying　a　50-fold　increase　in　molar　potency　in　this　smooth　muscle　type.　In　contrast,　a　100-fold　decrease　in　molar　potency　was　observed　at　bradykinin　receptors　in　intestinal　and　uterine　smooth　muscle　preparations.　Maximakinin　has　thus　evolved　as　a　＂smart＂　defensive　weapon　in　the　toad　with　receptor/tissue　selective　targeting.　Natural　selection　of　amphibian　skin　venom　peptides　for　antipredator　defence,　through　inter-species　delivery　by　an　exogenous　secretory　mode,　produces　subtle　structural　stabilisation　modifications　that　can　potentially　provide　new　insights　for　the　design　of　selectively　targeted　peptide　therapeutics.　©　2004　Elsevier　B.V.　All　rights　reserved.