Four different cimetidine dosage regimens--800 mg u.i.d. HS or nocte, 800 mg u.i.d. dinnertime, 400 mg q.i.d., and 800 mg b.i.d.--were investigated for the treatment of reflux esophagitis in three independent large-scale, double-blind, controlled multicenter trials in which more than 1100 patients participated. Analysis of the data shows that the percentage of endoscopic healing after 6 and 12 weeks of treatment was fairly constant in patients with the same endoscopic grade of severity of reflux esophagitis at the start of treatment, whether they were treated with 800 mg u.i.d. (HS or dinnertime), 800 mg b.i.d., or 400 mg q.i.d. Healing percentages after 12 weeks of therapy ranged from 79%-92% for grade I, from 65%-70% for grade II, and from 41%-54% for grade III. Differences within the three grades for the various treatment regimens did not reach statistical significance. Symptomatic improvement was evaluated with the Standardized Total Heartburn Index, which is based on frequency and severity of heartburn as well as on the number of patients in the study population experiencing heartburn at a given time in relation to the total heartburn load at the start of the study. All three treatment schedules resulted in a substantial reduction of the Standardized Total Heartburn Index. Treatment with cimetidine, 800 mg u.i.d., for 6-12 weeks was efficacious in the majority of patients with reflux esophagitis grade I-III. Symptom relief was superior with dosing after dinner time compared with dosing HS. A single dose of 800 mg administered after the evening meal approached the efficacy achieved with 400 mg q.i.d. Based on these objectives and symptomatic results, a u.i.d. cimetidine regimen appears to be the treatment of choice for the initial approach of a patient with reflux esophagitis. A u.i.d. regimen may enhance patient compliance, comfort, and safety as well as ease of prescription while also being less expensive.