Two immunoreactive neurotensin-related peptides generated by the action of endogenous protease(s) on protein substrates during acid extraction of avian tissues have been isolated from extracts of turkey skin and proventriculus. One was identified as the pentadecapeptide, H-Phe-Glu-Arg-Phe-Gln-Gly-Met-Arg-Thy-Arg-Gly-Pro-Tyr-Phe-Leu-OH and the other was its C-terminal octapeptide fragment. Each peptide showed partial homology to the C-terminal, biologically active region of avian neurotensin, and isolated preparations displayed pharmacologic activity at submicromolar concentrations. Synthetic preparations were shown to be indistinguishable from the native peptides during high pressure liquid chromatography (HPLC) and bioassay. Analysis by HPLC indicated that similar peptides could be generated in extracts of proventriculus, pancreas, small intestine, skin, heart, lung, and skeletal muscle. These results, establishing the presence of a neurotensin-related sequence which can be liberated from protein(s) by the action of tissue enzyme(s), suggest that peptide(s) similar to neurotensin may be rapidly formed in order to promote physiologic regulation in multiple tissue(s).