Background and Aims: We studied spontaneous gastroesophageal reflux (GER) induced esophageal distension using ultrasound imaging and its role in the genesis of esophageal symptoms before and during esomeprazole therapy. Methods: 10 controls and 10 GERD patients were studied using combined impedance, esophageal pH, manometry and ultrasonography before and during esomeprazole therapy. Physiologic data and symptoms were recorded for 2 hours following a standardized meal. From ultrasound images, the esophageal cross-sectional area (CSA) at the peak of GER induced distension was determined and compared between: controls versus patients; symptomatic versus asymptomatic GER episodes; and before versus during esomeprazole in GERD patients. Results: The mean lumen CSA is greater in the patients than controls (271 ± 71 mm² vs. 163 ± 56 mm², p=0.001), but no different among asymptomatic reflux episodes, ones associated with regurgitation (290 ± 110 mm²) and heartburn (271 ± 67 mm²). Eight chest pain episodes associated with reflux revealed a tendency towards larger mean esophageal distension (459 ± 40 mm²) compared to asymptomatic reflux (268 ± 70 mm², p=0.058). Following esomeprazole treatment, most GER episodes were non-acidic and asymptomatic except in 2 patients where cyclical reflux was associated with large esophageal distensions. Esomeprazole did not alter the lumen CSA during GER. Conclusion: Esophageal distension is greater in the GERD subjects compared to controls; however, it is unlikely that the GER induced distension of the esophagus plays a significant role in the genesis of heartburn sensation. Esomeprazole therapy does not alter the GER induced distension of the esophagus.