In 92 patients with duodenal ulcer, male cigarette smokers treated with cimetidine 1 g/day, 66.3% healed after four weeks. No differences were observed between healed and non-healed patients for age, symptom period before treatment, early onset (less than 30 years), multiple ulcers. In non-healed patients, more had a greater ulcer diameter (p = 0.0026) and more were heavy smokers (p = 0.0002). In non-healed patients, pentagastrin-induced maximal acid output, corrected for age, was higher than in healed patients (p less than 0.05). We confirmed the linear relationship between acid output and the number of cigarettes smoked per day (p less than 0.05). These observations suggest that cigarette smoking over a long period could stimulate the vagus. This would increase the functional parietal cell mass and explain the observed increase in pentagastrin-induced acid output.