The response of the small intestine of 6 normal subjects, 6 vagotomy control subjects, and 5 patients with postvagotomy diarrhea to a hyperosmolar liquid meal was investigated using small intestinal intubation. In the patients with postvagotomy diarrhea, the peak jejunal osmolality occurred earlier and was followed by a shorter small bowel transit time than in the vagotomy and normal controls. In the terminal ileum, both fasting and postprandial flow rates were higher in the group with postvagotomy diarrhea, compared with the other groups. This was associated with a high postprandial osmotic load to the colon, due in part to nutrient malabsorption. The postprandial flow of bile acids into the colon was not consistently related to diarrhea. Postvagotomy diarrhea is probably caused by rapid entry of fluid, electrolytes, and malabsorbed nutrients into the colon after meals. The rapid movement of an osmotic load through the upper jejunum, consequent upon the drainage operation, may be the critical trigger factor.