The concept of gastrointestinal hormones arose from experiments conducted by Bayliss and Starling in 1902 when they described the action of secretin, now known to be a peptide hormone produced in the small intestine that controls pancreatic secretion via the circulation (1). It is ironic that this description of a humoral regulatory system was reported a full 2 years before Pavlov was awarded the Nobel Prize for his theories on the control of organ function principally by nerves. Since the discovery of secretin, much has been learned about hormonal systems. Indeed, it seems that each year brings the identification of new hormones. In addition to their classical endocrine mechanism of action, gastrointestinal hormones have been described as functioning as local regulatory substances (paracrine agents), neurotransmitters, growth factors, cytokines, and other mediators of cellular activity. The observation of various clinical syndromes associated with overproduction of one or more of these hormones has provided insight into their importance in both physiologic and pathologic states. Nevertheless, these syndromes are rare, and thus most clinicians have had no need of a working knowledge about gastrointestinal hormones beyond the ability to recall a few of the features of exotic illnesses such as the Zollinger-Ellison or Verner-Morrison syndromes. Recent developments, however, have brought the topic of gastrointestinal hormones more clearly into focus for the practicing physician. One hormone, gastrin, has been the subject of considerable scrutiny in clinical studies.