By use of a newly developed electronic barostat, we investigated chyme-mediated intestinal regulation of gastric tone in a canine model. In this model the proximal (3 dogs) or distal (3 dogs) small intestine was luminally isolated, maintaining neuromuscular continuity. Gastric tone was measured by recording variations in the volume of air within an intragastric bag that was maintained at a constant pressure (2 mmHg) by the electronic barostat. The isolated intestinal loop was perfused constantly (5 ml/min) with either isotonic saline (control) or with test infusates (osmolality, 300 mosmol/kg; pH 7.4) of carbohydrate (maltose), protein (casein hydrolysate), fat (sodium oleate), or a combination of all three nutrients. The combined nutrient solution, infused into either the proximal or the distal intestine, profoundly inhibited gastric tone. Fat infused into the proximal intestine induced gastric relaxation, whereas protein had only a modest effect and carbohydrate had no effect. In contrast, in the distal intestine carbohydrate and protein markedly reduced gastric tone, whereas fat had no effect. We conclude that nutrients in the small bowel regulate gastric tone by a mechanism that is nutrient and region specific.