Glucagonlike substances in extracts of intestinal mucosa were already described in 1948 by Sutherland and deDuve (1), who used a bioassay technique for the identification. After the development of the first glucagon radioimmunoassays, Unger and co-workers (2,3) confirmed that intestinal extracts contained peptides that "crossreacted" in the glucagon radioimmunoassay [hence gut "glucagonlike immunoreactivity" (GLI)]. In 1968, the same group discovered that the gut GLIs consisted of at least two peptides, GLI I and II (4), both of which differed immunochemically from pancreatic glucagon and, therefore, necessarily had different chemical structures (4,5). Developments during the last decade in the field of peptide chemistry, particularly improved purification and sequencing techniques, have greatly advanced our knowledge of gut peptides, including the enteroglucagons, and the chemical structure of several of the members of this heterogenous group of peptides is now known. Furthermore, progress in the field of nucleotide and gene technology has also spread to this area of research, and although many problems remain unresolved, the progress made has sufficiently important implications to justify a review of the most recent advances.