The effect of sham feeding on pancreatic-polypeptide (PP) secretion was studied in 26 duodenal ulcer (DU) patients and in 8 healthy subjects. Modified sham feeding (MSF) by the 'chew and spit' technique induced a rapid increase in plasma concentrations of PP both in DU patients, 56 (2-138) pmol/l, and in the healthy subjects, 24 (2-45) pmol/l, median peak-increment and range. Four out of 26 DU patients and 2 out of 8 healthy subjects did not show any PP response to MSF. The PP response to MSF was abolished by pretreatment with atropine, or benzilonium, a quarternary anti-muscarinic agent with minimal cerebral actions. The PP response to MSF was not dependent on the gastric acid response, since a PP response to sham feeding was found in 13 out of 17 patients with selectively denervated parietal cell area, and thus, without acid response. During adequate sham feeding, in which the food is also swallowed but does not reach the stomach, the PP increment, 100 (81-129) pmol/l, was larger than during MSF in the same patients, 51 (8-78) pmol/l, median and total range, P less than 0.05, N = 7. No correlation was found between the PP and acid responses to sham feeding. It is concluded that cephalic stimulation provoked by tasting, chewing and swallowing is a major stimulus in the initial, rapid PP response during a meal; and that the PP cells are probably stimulated directly by a cholinergic mechanism.