The purpose of this investigation was to evaluate the long-term course of medically treated severe reflux esophagitis to determine if prolonged pharmacologic therapy was necessary to control symptoms. Twenty patients with chronic reflux esophagitis (mean duration, 13 years) achieved significant clinical improvement after acute intensive therapy with cimetidine and metoclopramide. During the 26-month follow-up period after remission, nine (45%) patients experienced a relapse of symptoms as drug dosages were tapered or discontinued, eight (40%) patients remained in remission, and three experienced a relapse of symptoms after a remission of longer than two years. Lower esophageal sphincter pressures were lower among patients who relapsed compared with patients with prolonged remission (4.9 vs 13.2 mm Hg). Drug requirements to maintain symptom control were antacids alone in five patients, bedtime H2-blocker in five, full-dose H2-blocker in four, and bedtime metoclopramide (10 mg) plus an H2-blocker in six. Moreover, the symptoms of three patients receiving full-dose H2-blocker therapy were controlled with antacids alone for two years, until relapse occurred. In conclusion, some patients with severe, long-standing reflux esophagitis will have a lasting response to short-term intensive medical therapy. Long-term intensive therapy may be unnecessary in many patients. Patients with lower sphincter pressures may have a higher likelihood of symptomatic relapse.