Clinical and experimental studies have shown that acid and bile reflux are increased in patients who have Barrett's esophagus. The combination of both seems the key factor in the pathogenesis of Barrett's esophagus. This factor has been confirmed by immunohistochemical studies that show that environmental factors, such as acid and bile, are involved in the pathogenesis of Barrett's esophagus. There is a critical pH range between 3 and 6 in which bile acids exist in their soluble, un-ionized form; can penetrate cell membranes; and accumulate within mucosal cells. At a lower pH, bile acids are precipitated, and at a higher pH, bile acids exist in their noninjurious ionized form. Thus incomplete gastric acid suppression, as is the case with most medical treatment regimens for gastroesophageal reflux, may in fact predispose to the development of Barrett's esophagus.