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Cigarette smoking has been linked to an elevated incidence of duodenal ulcer disease in smokers, although the mechanism is unclear. In 23 young normal subjects single or double secretin tests were performed during non-smoking and smoking periods. Cigarette smoking inhibited the secretion of pancreatic juice and bicarbonate in light smokers (< one pack/day for < three years). Heavy smokers (> one pack/day for > three years) exhibited depressed pancreatic secretory rates during non-smoking periods. Inhibition of pancreatic alkaline secretion by cigarette smoking could be the link between the habit and duodenal ulcer disease.