The modern concept of GERD did not emerge until 1935, when Winkelstein suggested that esophagitis was caused by the action of gastric juice. The term reflux esophagitis, however, did not appear until 1946, when it was introduced by Allison. In the 1950s, GERD was thought to be caused by abnormal ana-tomic, mechanical factors associated with a sliding hiatal hernia. At the same time, many reports appeared confirming the existence of a lower eso-phageal sphincter (LES) that maintained a pressure barrier between stomach and esophagus. In the 1960s, the concept became widely accepted that the major determinant of GERD was "LES incompetency" caused by a feeble or atonic LES. Beginning in the 1970s, the cumulative findings carted doubt that a single factor, such as low resting LES pressure, could universally account for GERD production in all patients. After that, the consensus emerged that GERD is caused by a multifactorial process. The multiple determinants in the pathogenesis of GERD are described by Dodds as follows: 1) efficacy of antireflux mechanism, 2) volume of gastric con-tents, 3) character of refluxed material, 4) efficiency of esophageal clearance, 5) resistance of the eso-phageal mucosa. In these determinants, GER and acid clearance are major factors in the patho-physiology of GERD. I) Mechanisms of gastroesophageal reflux Three mechanisms associated with GER were revealed: 1) transient LES relaxation, 2) intraab-dominal pressure transients, 3) spontaneous free GER. Transient LES relaxation accounted for greater num-ber in controls than GER patients. The latter two mechanisms were easily associated with a low resting LESP of GERD patients. II) Gastric contents In order to cause esophageal epithelial changes resulting from GER, the refluxed materials, such as gastric acid, pepsin, and bile, must have some potency to injury. However, there was no significant differ-ence between controls and GERD patients in analytic studies of each materials. In regard to the develop-ment of GERD by Helicobacter Pylori (HP), no corre-lation between the presence of HP and esophagitis was found. III) Acid clearance Delayed esophageal acid clearance exists in GERD patients, that is caused by impaired primary peristal-sis, sleep, or insufficiency of LES relaxation. IV) Esophageal mucosal resistance The ability of esophageal mucosa to withstand injury and undergo repair may be related to mucus, bicarbonate ions, and intercellular junctions. V) GER in patients with mucosal discoloring type The severity of GERD in these patients is mild. The incidence of GER episodes in the patients was higher than normals according to our results of 24 hour pH monitoring. It is difficult to distinguish this type from the scarring stage of erosive ulcerative GERD by endoscopy.