There are conflicting reports on the influence of cigarette smoking on healing in patients with duodenal ulcer; some studies show an adverse effect on healing rate and others no effect. This study reports the influence of smoking on short-term healing and relapse rate in 135 patients with duodenal ulcer who were treated with cimetidine (90), ranitidine (25), and oxmetidine (20), all powerful H2-receptor antagonists. Ulcer healing and relapse were documented endoscopically and all studies were performed in a double-blind manner. In the short term, 95% of nonsmokers healed compared with 63% smokers (p less than 0.01) and there was a positive correlation between failure to heal and number of cigarettes smoked. During a 12-mo follow-up examination after healing and on no treatment, 53% of nonsmokers and 84% of smokers relapsed (p less than 0.01). These results show that smoking adversely affects healing of duodenal ulcer with H2-receptor antagonists and that continued smoking leads to a higher relapse rate.