Pancreatic polypeptide is said to be a marker of vagal tone in duodenal ulcer. To determine whether pancreatic polypeptide levels are related to the course of duodenal ulcer, we studied acid and pancreatic polypeptide responses to insulin in 80 patients with duodenal ulcer disease: 40 with unoperated duodenal ulcer and 40 with proximal vagotomy. Data were analysed in accordance with the presence of an ulcer (active disease) and, when present, in accordance with the ulcer healing on medical treatment (cimetidine, 1 g/day for 4 weeks). In both groups acid and pancreatic polypeptide responses to hypoglycaemia were slightly correlated (r = 0.38) (p less than 0.05). The basal pancreatic polypeptide level was higher in patients with active disease than in those with inactive disease, who had a basal level similar to that of normal subjects of the same age range. Like the insulin-stimulated acid secretion, the pancreatic polypeptide response to insulin hypoglycaemia was higher in patients with active disease than in those with inactive disease (p less than 0.05): 26.1 +/- 3.9 versus 20.1 +/- 4 nmol/l/120 min, respectively, in unoperated patients and 34.8 +/- 2.2 versus 24.3 +/- 2.5 nmol/l/120 min, respectively, after proximal vagotomy. In active disease the pancreatic polypeptide response to insulin hypoglycaemia was higher in subjects whose ulcer did not heal further after cimetidine therapy than in those whose ulcer did. These data suggest that the pancreatic polypeptide response to insulin is an indicator of duodenal ulcer activity and is related to the treatment efficacy. These relationships are partly mediated by increased vagal tone.