AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy. AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease (NERD) patients. METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 weeks, were included in this study. All patients underwent 24 h combined impedance-p H on rabeprazole. The symptom index (SI) was considered to be positive if positive ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal The occurrence rate of reflux symptoms was significantly more in reflux molecules (46.7%) than in distal ones (5.7%) (P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes (38.5%) and proximal ones (20.5%) (NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflu With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptom between (33.0%) than in distal reflux ones (3.3%) proximal reflux episodes (29.4%) and distal ones (14.3%) (NS) .CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.