The influence of caloric load and nutrient composition on small intestinal satiety was investigated in six dogs with chronic esophageal fistulas. Dogs received small bowel infusion of a mixed nutrient liquid meal, a fat, carbohydrate, and a protein solution over two hours. Each infusion was given over a range of caloric densities which represented between 0 to 20% of the total 24 h caloric requirement for each animal. Satiety was measured by sham feeding at the end of the infusion. Infusion of 0.25 cal/ml (equivalent to 5% of the 24 h caloric requirement) of a liquid mixed nutrient meal (Isocal) significantly suppressed sham feeding (volume sham fed: control 265 +/- 28 ml/min; Isocal 0.25 cal/ml 218 +/- 52 ml/min, p < 0.05). Oleate and dextrose polymer also significantly reduced sham feeding at a caloric concentration of 0.25 cal/ml (volume sham fed: control 265 +/- 28 ml/min; oleate 112 +/- 28 ml/min; oleate 112 +/- 9 ml/min; dextrose polymer 190 +/- 11 ml/min), whereas peptone did not significantly suppress sham feeding until a solution with 0.5 cal/ml was given. These studies demonstrate that caloric load of intestinal nutrients must reach a threshold to produce satiety in sham feeding dogs. The threshold caloric load is different for the three nutrient groups, with fats requiring the lowest caloric load to produce satiety. These provide insight into the mechanisms by which small intestinal signals might contribute to regulation of the inter-meal interval.