The degree of esophageal mucosal injury that occurs in patients with gastroesophageal reflux disease depends on duration of exposure and pH of the refluxate. Evidence suggests that an intraesophageal pH of less than 4.0 directly correlates with the degree of mucosal injury. The advent of acid secretory inhibitors such as the histamine2-receptor antagonists (H2RAs) and, more recently, the proton pump inhibitors (PPIs) has revolutionized the treatment of patients with reflux disease. However, the evidence linking the degree of mucosal damage to pH of the refluxate has prompted investigators to reevaluate the effectiveness of these agents. The PPIs are significantly more effective than the H2RAs in achieving and sustaining an intragastric pH above 4.0. The results of clinical trials performed with the PPIs indicate a faster rate of healing of erosive esophagitis and of symptom relief than treatment with H2RAs.