Little is known about the causes of heartburn in patients with gastro-esophageal reflux disease (GERD). Visible epithelial damage is seldom associated with symptom severity, evidenced by the significant symptom burden in patients with non-erosive reflux disease (NERD) compared to patients with erosive reflux disease (ERD) or Barrett’s esophagus (BE). We studied the distribution of mucosal nerve fibers in patients with NERD, ERD, and BE, and compared the results with those of healthy subjects.