From the mucosa of the gastrointestinal tract a number of peptides can be extracted, which are glucagon-like in their behavior towards antisera raised against the pancreatic hormone. The biochemistry and physiology of these peptides are critically reviewed. Although important advances have been made, facilitated by improved praparative and analytical techniques, many problems remain unresolved. It is, however, now well established that a peptide, which is indistinguishable from true, pancreatic glucagon (NW 3,485) is found in extrapancreatic gastrointestinal tissue from all species investigated. While abundant in dogs, especially in the gastric mucosa, much less is found in extra-pancreatic tissues of man and pig. Results from studies in dogs are therefore not necessarily relevant to other species. Human and porcine gut, however, contain other glucagon-like peptides (gut-type glucagon, enteroglucagon, gut GLI), one of which resembles true glucagon (MW 3,485) in its biological activity, but a definite physiological role for these peptides has not yet been established. The recent isolation and purification of one of the latter peptides undoubtedly will facilitate greatly future research in this field.