Dermenkephalin molecules corresponding to the predicted prodermorphin heptapeptide were first isolated from skin extracts of the South American frog Phyllomedusa sauvagei. It acts as a highly potent and fully selective agonist for the delta opioid receptor. Dermenkephalin has no structural features in common with the sequences any of the hitherto known opioid peptides. It should be a useful tool for identifying conformational determinants for high affinity and selective binding of opioids to the delta receptor.