The results of both phylogenetic and ontogenetic investigations of the evolution of the disseminated NE cells of the GIT have shown that they are members of the large NE system, consisting not only of the GI-NE cells but also of the neurons of the central and peripheral nervous system with their nerve fibers (the peptidergic nervous system) and of the classic, solid endocrine glands. The evolutionary studies also have shown that these three major parts of the NE system are closely interrelated to each other. The most original part is obviously the neuronal one, occurring already in the most primitive animals (the coelenterates). The next step in the evolution of the NE system is the appearance of NE cells of open type in the mucosa of the alimentary tract. Such gut NE cells are present in the most highly developed invertebrates, both Protostomian and Deuterostomian, and they persist and become even more diversified in the vertebrates, including humans. The presence of GEP-NE glands of classic, solid type seems to be a feature restricted to the true vertebrate animals. The earliest vertebrates (the jawless fish and the cartilaginous fish) often offer the best pieces of evidence for the manner in which the parenchyma of such a GEP-NE gland, notably the islets of Langerhans, is formed from disseminated NE cells of open type in a mucosa, in this case that of the gut.