We determined serum pepsinogen I (PG I) levels by radioimmunoassay in 472 patients with duodenal ulcer and 141 normal subjects to investigate whether serum PG I levels were related to cigarette smoking, and in 225 patients to determine whether the recurrence of duodenal ulcer was related to serum PG I levels or cigarette smoking. Serum PG I levels were not influenced by cigarette smoking in either patients with duodenal ulcer or normal subjects. The recurrence rate of duodenal ulcer not under maintenance therapy was significantly higher in hyperPG I patients than in normoPG I patients, regardless of their smoking habits. Only in hyperPG I patients was the recurrence rate in smokers higher than in nonsmokers. Patients under maintenance therapy showed similar results. Multilogistic regression indicated that hyperPG I had a greater effect than cigarette smoking on ulcer recurrence. These findings indicate that serum PG I levels are not influenced by smoking, and the important characteristic in patients with recurrent duodenal ulcers is the increased serum PG I levels.