DESCRIPTION: The gastroesophageal junction is the first portal through which noxious gastric contents must pass if they are to cause injury to the upper aerodigestive tract. When reflux occurs excessively and clearance of reflux is impaired, patients can develop esophagitis, ulcers, stricture, adenocarcinoma, laryngitis, and aspiration pneumonia. Unfortunately, the mechanisms for initiating and suppressing reflux and the factors contributing to the altered clearance of the refluxate are poorly understood. The specific objectives of this subproject are to explore the following hypotheses: 1). Intragastric pressure is a major determination of whether reflux occurs, with reflux patients having lower threshold pressures for triggering reflux. 2). Afferent sensory pathways in the cardia of the stomach are important in triggering GERD. Agents can be delivered endoscopically to block these pathways and inhibit GER. 3). Esophageal longitudinal muscles play an active role in the reflux event. 4). Esophageal acidification alters the function of longitudinal esophageal muscles, so as to contribute to forming a hiatal hernia. 5). Longitudinal esophageal muscle function during primary and secondary peristalsis is abnormal in patients with reflux disease, and these abnormalities contribute to disturbances in esophageal bolus clearance.