To investigate the mechanisms by which intestinal carbohydrate affects eating behavior, seven fasted, healthy male volunteers received intraduodenal infusions of glucose or saline over a 90-min period while blood glucose levels were matched by use of intravenous glucose and saline infusions. A second study examined the effect of intraduodenal glucose on eating behavior when the gastrointestinal hormone response was inhibited by intravenous octreotide. Intravenous glucose infusion did not affect hunger or satiety. In contrast, intraduodenal infusion of glucose suppressed hunger, increased fullness and satiety ratings, reduced energy intake, and resulted in higher plasma insulin responses compared with the intravenous glucose infusion. Octreotide abolished the plasma insulin response to intraduodenal glucose and reversed the changes in ratings and eating behavior. This study has shown that the effects of intestinal glucose on appetite are not mediated via an increase in blood glucose but are likely to reflect small intestinal stimulation of release of either insulin or intestinal incretins.