Publisher Summary Several years of search for a putative factor in brain, which activates opiate receptors, has culminated in the isolation of two pentapeptides, Met-enkephalin [Ia] and Leu-enkephalin [Ib] from guinea pig brain. Both have been synthesized and showed typical opioid activity in vitro and analgesic effects in vivo. This chapter reviews Peptide hormones that are of other than hypothalamic or pituitary origin. The structures of seven species-different calcitonins have been determined. Conventional syntheses of porcine, human and salmon calcitonin provided large supplies of homogeneous peptides for physiological, pharmacological, and clinical investigations. Salmon calcitonin is far more potent in man than human calcitonin that may be attributable to increased metabolic stability. Secretion of calcitonin from porcine thyroid glands is effected by activation of C-cell adenyl cyclase by either ionized Ca or by hormones (glucagon, gastrin, CCK, epinephrine). Calcitonin effects are age-dependent and are very low in normal adult humans. 6-Lipotropin is thus another example of a second order prohormone, that is, a well-defined peptide hormone serving as a precursor for a smaller peptide with entirely different hormonal activities. The characterization of the opioid peptides may suggest new approaches to the development of nonaddictive analgesics.