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AIM: To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD).METHODS: Eighteen patients with erosive esophagitis,10 patients with non-erosive reflux disease (NERD),and 18 normal asymptomatic volunteers were enrolled.Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion.Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment.RESULTS: The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals.CONCLUSION: Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.