OBJECTIVE The aim of this dose-response study was to compare the effectiveness of 10 mg, 20 mg, and 40 mg of pantoprazole with that of placebo tablets in the healing and symptom relief of gastroesophageal reflux disease associated with erosive esophagitis, and to determine the optimal dose. METHODS A total of 603 patients with endoscopically confirmed (Hetzel-Dent scale) erosive esophagitis of grade 2 (64.5%) or grades 3 or 4 (35.3%) were enrolled in a double-blind, multicenter study and randomly assigned to receive pantoprazole (10 mg, 20 mg, or 40 mg) or placebo, administered once daily in the morning, for 4 or 8 wk depending on healing. RESULTS The healing rates after 4 wk for placebo and pantoprazole 10 mg, 20 mg, and 40 mg/day were 14%, 42%, 55%, and 72%, respectively (p < 0.001 for all doses of pantoprazole vs placebo). Cumulative healing rates after 8 wk for placebo and pantoprazole 10 mg, 20 mg, and 40 mg/day were 33%, 59%, 78%, and 88%, respectively (p < 0.001 for all doses of pantoprazole vs placebo). The 40-mg pantoprazole dose produced greater rates of healing and earlier healing of esophagitis than either the 10- or 20-mg dose, regardless of severity. Pantoprazole, at any dose, was significantly more effective than placebo in relieving reflux symptoms. Patients on pantoprazole 40 mg experienced relief of symptoms on day 1 of treatment. No serious treatment-related adverse events occurred. CONCLUSIONS Pantoprazole was safe and effective for healing erosive esophagitis and provided rapid symptomatic relief. These results indicate that pantoprazole offers a new option for treatment of erosive esophagitis. Among the three doses studied, the 40-mg dose was the most effective.