Emotional stress (ES) has been proposed as a possible factor in the pathogenesis of duodenal ulcer (DU) disease. Modem, well-controlled studies on the effect of ES on gastric acid secretion (GAS) in both normal healthy subjects and patients with inactive DU are lacking. Ten normal (N) men and 10 men with inactive DU were observed on 2 separate days. In random order, subjects either underwent dichotomous listening (DL) to induce stress or a control (non-DL) test. In addition to measuring GAS in 15-min periods, heart rate and blood pressure were measured every 7.5 min, and visual analog scale measures of emotion (relaxation, anxiety, anger, tension, and depression) were monitored. Subjects underwent 2 separate study days, 1 h of a basal period followed by 1 h of a DL session or 1 h of a basal period followed by 1 h of a non-DL control session; the order of the days was randomized. In both N and DU emotional stress by DL induced these parameters significantly: increased heart rate; raised systolic and diastolic blood pressures (p < 0.01); increased anxiety, anger, and tension (p < 0.03); and decreased relaxation (p < 0.01). The non-DL control test did not alter cardiovascular or emotion measures in either group. While ES did not alter GAS in N subjects, ES increased GAS when compared to the basal state (p < 0.02) and when compared to the control test (p = 0.07). We conclude that in N subjects, DL induces mental and cardiovascular evidence of acute stress but fails to alter GAS, and in patients with inactive DU, ES resulted in similar mental and cardiovascular changes as observed in normal subjects, yet was accompanied by an increase in GAS. These preliminary findings suggest that acute ES stimulates GAS in patients with DU disease.