The effect of smoking on the pH of the duodenal bulb was studied in 10 normosecretors and 10 hypersecretors using a Beckman pH electrode. The pH was monitored during three study periods, basal, smoking, and postsmoking, of 1 hr each. The pH remained below 3.5 significantly longer during the smoking period compared to the basal period for both groups. The bulbar pH remained under 3.5 during the smoking period longer in the hypersecretor group compared to the normosecretor group (60 versus 20%). Hypersecretors who were smokers exhibited acidic bulbar pH values longer and more consistently than hypersecretor-nonsmokers during smoking. In 5 hypersecretors with data for both bulbar pH and bicarbonate output, inhibition of bicarbonate output during smoking was generally associated with acidic pH values in the bulb. These observations suggest that the association between cigarette smoking and peptic ulcer disease may be attributable to, in part, the persistently acidic pH values in the duodenal bulb during smoking. This study further suggests that the degree and the duration of acidification of the duodenal bulb during smoking are influenced by the secretory and the smoking status of the subject.