Esophageal mucin secretion in patients with reflux esophagitis (RE) is significantly impaired. Rabeprazole augments gastric mucin secretion. We have studied, therefore, the effect of rabeprazole on esophageal mucin secretion in patients with RE. The study was conducted in 15 patients with RE treated with rabeprazole (20 mg QD) for 8 weeks. Esophageal secretions were collected during consecutive infusions of initial NaCl, HCl/Pepsin (HCl/P), and a final NaCl, using a specially designed esophageal catheter, before and after therapy. Mucin was measured using standard methodology. After rabeprazole administration esophageal mucin concentration as well as secretion increased during perfusion with initial saline (P < 0.01), HCl/P (P < 0.02), and concluding saline (P < 0.001). Stimulation of esophageal mucin secretion by rabeprazole may indicate that the mechanisms governing its secretion are similar to those implicated in gastric mucin output. Enhancement of esophageal mucin secretion by rabeprazole may translate into esophagoprotective potential in patients with reflux esophagitis.