Preceding phylogenetic studies on the occurrence of insulin have shown--e.g. by bioassays and immunocytochemical procedures--that insulin producing B-cells are present in all vertebrates and even in several invertebrates, both protostomian and deuterostomian. The most original B-cells are obviously endocrine cells of open type, situated in the mucosa of the alimentary tract. Moreover, the results of these studies show that insulin is not only a polypeptide hormone of considerable age but also that the insulin molecule seems to have been kept surprisingly stable during evolution. Best known of all non-mammalian insulins is that from the hagfish, Myxine glutinosa. It is probably the most original insulin of all in the vertebrate series. Both the amino-acid sequence and the three-dimensional structure of the dimer of hagfish insulin differ only little from those of pig insulin. The biosynthesis occurs via proinsulin and is also in most respects similar to mammalian insulin biosynthesis. There are, however, some differences. Although it readily crystallizes as tetragonal bipyramids, hagfish insulin does not form hexamers. In a test system, with isolated rat fat cells, its binding affinity is 23% and its potency 5% of that of pig insulin, a discrepancy indicating a "partial antagonism" on the receptors. Although the conversion of proinsulin to insulin seems to occur in the secretion granules, they contain no crystalline cores. Since a strictly tryptic-like enzyme was found to destroy hagfish insulin rapidly, the enzyme converting proinsulin to insulin must--in addition to a carboxy-peptidase-B-like activity--have a different specificity in Myxine.