Although H2-receptor antagonists have been the mainstay of therapy for gastroesophageal reflux disease (GERD), none of these agents has been approved by the FDA as effective in healing lesions. Since proton pump inhibitors may be associated with long-term disadvantages, a healing regimen with cimetidine would be useful clinically. This multicenter, randomized, double-blind study was conducted to evaluate the efficacy of cimetidine 800 mg b.i.d. in healing lesions and in providing symptomatic relief in patients with ulcerative or erosive esophagitis. Patients with greater than or equal to 8 heartburn episodes during a 1-week screening period, reflux confirmed by esophageal pH monitoring, and esophageal ulcers or erosions confirmed by endoscopy were randomized to treatment with placebo or cimetidine for 12 weeks. Cimetidine provided significantly greater (p less than 0.01) improvement (74% vs. 51%) and complete healing (67% vs. 36%) of esophageal lesions than did placebo. In these patients with erosive or ulcerative esophagitis, the median time to achieve 24 h without heartburn was 13 days with cimetidine and 30 days with placebo (p = 0.01). The mean heartburn severity score in the cimetidine group decreased rapidly during the first week and was consistently lower than in the placebo group. Cimetidine, 800 mg twice daily, is effective in promoting healing of esophageal ulcers and erosions and in providing heartburn relief in patients with symptomatic erosive/ulcerative GERD.