Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day) were evaluated in a double-blind, randomized multicenter study in 474 symptomatic patients with erosive ulcerative reflux esophagitis. A total of 238 patients were treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinner-time. Relief of symptoms was significant in all patients after six and 12 weeks and not different in both treatment groups. Overall endoscopic healing was significantly better in the famotidine 40 mg twice a day group compared with 20 mg twice a day at week 6 (58% versus 43%; P < 0.05) and at week 12 (76% versus 67%; P < 0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a day in those patients not healed after 12 weeks did not result in further symptom relief or in significantly better overall healing. The differences in efficacy of these two doses were more pronounced with increasing severity of esophagitis. Analyzed by grade of esophagitis at entrance, healing was significantly better with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades III and IV, and at week 24 for grade IV esophagitis. The results show that in the treatment of erosive/ulcerative reflux patients famotidine 40 mg twice a day is more effective and achieves faster healing than famotidine 20 mg twice a day.