Because of a newly developed model of esophageal perfusion in humans, the authors could study the role of esophago—salivary reflex in salivary neutral and acidic mucin output. The basal rate of neutral mucin output was 0.24 ± 0.06 mg per minute. Placement of intraesophageal tubing and inflation of balloons resulted in a highly significant increase in salivary mucin output (2.10 ± 0.22 mg per minute; p < 0.00001). However, implementation of esophageal perfusion with saline resulted in a significant decline of salivary mucin output (1.28 ± 0.10 mg/mL NaCl4 versus 2.08 ± 0.24 mg/mL NaCl1; p < 0.001). Esophageal perfusion with hydrochloric acid prevented the decline of salivary mucin output observed during perfusion with saline, whereas infusion of hydrochloric acid/pepsin resulted in a significant enhancement of salivary mucin output (2.89 ± 0.31 mg per minute; p < 0.01). Therefore, mechanical and chemical stimulations resulted in an overall 9-fold and 12-fold increase in the rate of salivary mucin output over the basal value, respectively. The basal rate of acidic mucin secretion was 0.26 ± 0.06 mg per minute. After placement of intraesophageal tubing, inflation of balloons, perfusion hydrochloric acid, or hydrochloric acid—pepsin solution, a significant enhancement in the rate of salivary acidic mucin output, similar to that observed during measurement of neutral mucin, was observed. Therefore, during mechanical and chemical stimulation, the rate of salivary acidic mucin output increased 7.3-fold and 11.1-fold over the basal value, respectively. A significant increase of salivary mucin output, especially under the impact of esophageal stimulation with acid and pepsin, indicates that mucin may play an important role in esophageal preepithelial defense mechanisms.