AbstractOn 94 patients with duodenal ulcer and 44 controls, parietal cell mass (PCM), as derived from pentagastrin‐stimulated peak acid output (PAO), was significantly greater in chronic cigarette smokers than in non‐smokers. Smokers and non‐smokers did not differ in their fasting and postprandial serum gastrin concentrations, and in the frequency of familial ulcer, although basal acid output (BAO) and BAO/PAO were significantly higher in smokers, suggesting the presence of hypervagotonia. Chronic hypodermic administration of depot nicotine in rats resulted in significant dose‐dependent increase in PAO and PCM as determined histologically, supporting the results of the human studies. Acute administration of nicotine, however, did not cause any increase in acid output, indicating that it had no effect on parietal cell function. Chronic nicotine administration also led to significant increase in antral G cell mass as determined by immunohistochemical labeling, and in peptone‐stimulated serum gastrin. The effects on PCM and G cells were abolished by the simultaneous administration of atropine. Nicotine induced gastric electrical and motor activities in rats similar to those induced by carbachol, and the effects of both agents could be blocked by atropine. Nicotine had no effect on gastric mucosal blood flow in rats as estimated by neutral red clearance. We conclude that cigarette smoking in man and chronic nicotine administration in rats cause parietal cell hyperplasia, plus, in rats, G cell hyperplasia, possibly through a cholinergic