We have isolated, purified and partially characterized a polypeptide weighing approximately 7,000 daltons which can be extracted by mineral acid from porcine desiccated, defatted pancreas. This polypeptide will cross-react with antisera prepared against the haptens of synthetic beta endorphin and will displace labeled Naloxone or enkephalinamide from rat brain cell binding sites in vitro. This material will also, like beta endorphin, demonstrate analgesia in the "mouse tail flick" assay, when injected intracerebroventricularly at a concentration of 50 pg/mouse. This analgesia is totally overcome by intravenous Naloxone. When this material is injected at a concentration of approximately 100 pg intravenously, it will also demonstrate approximately 20 plus minutes of analgesia in the tail-flick assay; beta endorphin does not demonstrate analgesia intravenously unless it is used at a concentration of 20,000 nanograms per mouse! The analgesia at this dose of beta endorphin only lasts 4 minutes. Volunteers, stressed by exercise (i.e., jogging) have been found to increase their circulating concentration of endorphin determined by RIA (New England Nuclear) from 10 to 30 femtomoles/ml. Eighty-five percent of this increment has a molecular weight twice the size of the pituitary endorphin and appears identical with that of the pancreatic and placental endorphin described above. We have purified this circulating polypeptide and found that it posesses the same properties (including pharmacologic properties) as does the pancreatic endorphin. From the above we conclude that the pancreas contains an endorphin polypeptide which survives in the circulation and has considerable effect therein in terms of analgesia in contradistinction to classical beta endorphin which appears to be a messenger for communication within the brain itself.