In order to investigate the intestinal phase of pancreatic polypeptide (PP) release, the hormonal response to food and cerulein was measured in 19 patients with truncal vagotomy and total gastrectomy (10 with simple esophagojejunal anastomosis and 9 with an additional duodenojejunal anastomosis) and in 7 healthy subjects. After gastrectomy, the early peak of the physiologic biphasic PP response to food was lost but the late predominant phase was unchanged so that the overall postprandial release of the hormone was not significantly lowered. Gastrectomized patients with duodenal bypass had postprandial serum levels only slightly lower than those of patients with preserved duodenal transit of food. Serum PP response to cerulein stimulation was significantly lower in vagotomized patients than in healthy subjects. However, in operated patients as well as in controls, cerulein infusion did induce a rapid increase of plasma PP, followed by persistently elevated levels. The PP response to cerulein was abolished by atropine pretreatment. Our findings indicate that the intestinal phase of meal-stimulated PP response is not dependent on the integrity of vagal pancreatic innervation and that the preservation of the duodenal transit of food after total gastrectomy is not crucial for the maintenance of the enteroinsular axis.