To further define the influence of cigarette smoking on the pathophysiology of gastroesophageal reflux disease, studies were done to evaluate acid clearance in the esophagus and the salivary titratable base secretion of chronic smokers as compared to those of nonsmokers, and to ascertain the acute effects of smoking on these variables. Eight nonsmoking volunteers and 16 cigarette smokers without symptoms of gastroesophageal reflux disease were studied. All studies were initiated after a 6-hour fast, with the smokers also having refrained from smoking. Of the 16 smokers half smoked three cigarettes in the course of the experiments and half did not smoke. The immediate effects of cigarette smoking were a prolongation of the acid clearance time and a diminution of the secretion of salivary titratable base. However, both of these effects were overshadowed by greater baseline differences between the populations of smokers and nonsmokers. As a population the smokers had only 60% of the titratable base secretion of nonsmokers and acid clearance times that were 50% longer than those of nonsmokers. These effects were presumably long-lasting effects of cigarette smoking, although the duration of the effect was not defined. The observed differences in acid clearance are most likely the result of diminished salivary base secretion, since good correlation existed between these parameters.