The stomachs of six healthy volunteers were intubated with a Levine tube. In addition, a thin polyethylene tube was placed in the proximal jejunum or in the proximal duodenum. After a 1-h period with no perfusion the intestine was perfused for 2 h with 7% liver extract (LE) (pH 5.5; 380 MOsm/kg water) at a rate of 100 ml/h. In control tests 200 ml of 0.9% physiologic saline solution were used as perfusate. Reflux to the stomach was determined by addition of radioactive B12 to the perfusates. Plasma gastrin, gastric acid, and pepsin levels were measured in 15-min periods. During perfusion of the proximal jejunum only pepsin outputs were increased significantly. During duodenal perfusion of LE, gastric acid and pepsin outputs were increased to 31% and 73% of maximal pentagastrin stimulation, respectively. Controls showed no changes in gastric secretion. Plasma gastrin levels were not elevated after jejunal or duodenal perfusion. These results confirm that the intestinal phase of gastric secretory stimulation does exist in humans. Furthermore, it appears that the major portion of this stimulation originates from the duodenum and is not gastrin-dependent.