Gastrointestinal modulation of islet cell hormone release is important in the maintenance of the post-prandial glucose homeostasis in man. Our published observations have suggested that partial gastrectomy in subjects who have normal intravenous glucose assimilation (k values) results in a "pseudodiabetic" state characterized by diminished insulin levels relative to the prevailing glucose concentration early after oral or intrajejunal glucose. In addition, these subjects showed marked elevation of glucagon-like immunoreactivity (GLI) compared with matched control subjects. Matched pyloroplasty subjects did not demonstrate a comparable deficit in early insulin release. We propose to perform suitable glucose tolerance tests (GTT) on a larger number of subjects with different gastric operations and on matched control subjects. Use of a pancreatic specific glucagon antibody should allow us to determine the source of the abnormal GLI and its role in the pathogenesis of this "pseudodiabetic" state. A second oral GTT in antrectomized subjects after pretreatment with purified secretin which is known to augment insulin release and to suppress glucagon, and to be diminished after partial gastrectomy, should clarify this hormones's proposed role in the abnormal glucose assimilation. A controlled, systematic, prospective study, in dogs, on the sequential effects of pyloroplasty, antrectomy and vagotomy on glucose tolerance is proposed concurrently to define the neural and hormonal control of glucose-responsive gastrointestinal modifiers of islet cell hormone release and their role in the pathogenesis of post-gastrectomy "pseudodiabetes".