To study whether the vagus sustains basal secretion and stimulates acid and pepsin differently in duodenal ulcer (DU) and non-DU, we tested 144 patients with DU and 92 nonulcer controls, using 1-hr basal secretion followed by 15 min of modified sham feeding (MSF) and after 1 hr followed by a reference maximum elicited by 6 micrograms/kg pentagastrin given subcutaneously and observed for another 1 hr. Of all subjects, 97.5% responded to MSF by raising basal acid output (BAO) at least 15%. MSF added amounts of acid equal to 26-30% of peak acid output and 30-43% of peak pepsin output, regardless of diagnosis or level of basal secretion (including hypersecretors). Speed and duration of responses were similar in DU and controls. MSF did not substantially alter serum gastrin. Males secreted more acid and pepsin than females under all conditions, differences that persisted in DU but not in controls when outputs were corrected for body weight. Male DU but not female DU patients secreted more than corresponding controls. Sham feeding is an effective stimulus with similar characteristics in controls and DU patients. There was no evidence for saturation of vagal pathways in basal hypersecretors. MSF stimulation does not appear to involve gastrin. Hypersecretion in DU derives largely from responses in male DU.