Scarce data exist on the medical treatment of patients with peptic esophagitis who are non-responders to conventional or higher doses of H2-blocker agents, and no controlled trial on such patients has been published so far. We conducted a randomized single-blind study on the effects of 1 g sucralfate four times daily (n = 8), a mucosa-protective agent, versus 40 mg famotidine twice daily (n = 8), a new H2-blocker agent, administered for 12 weeks, in the treatment of peptic esophagitis (grades I to IV in accordance with Savary and Miller) refractory to a 6-month therapy with ranitidine at a dosage of 150 or 300 mg twice daily. Complete healing of the esophageal lesions was observed in none of eight patients receiving sucralfate, as compared with five of eight taking famotidine (p less than 0.05, Fisher exact test). Three of eight patients treated with sucralfate and three of eight with famotidine had complete disappearance of symptoms, whereas improvement was observed in two and three of eight, respectively (p less than 0.05 in both cases). We conclude that anti-secretory therapy is more effective than mucosal protection in the treatment of refractory peptic esophagitis.