Evidence for an entero-insular axis is based upon studies showing that amino acids as well as glucose cause a greater and earlier release of islet cell hormones when administered via the gastrointestinal tract than occurs with comparable elevations in the plasma concentrations of the nutrients given intravenously. The ability of several gastrointestinal hormones to elicit immediate augmentation of insulin and glucagon secretion has been established. Gastrin, secretin, and pancreozymin in dogs all produce an immediate rise of insulin to a peak one minute after injection, but the response to gastrin is quantitatively trivial, while that to secretin is modest. However, pancreozymin elicits substantial release of both insulin and glucagon, and augments the insulinogenic and glucagonogenic effects of amino acids. The physiologic implications of such studies are considered.