As part of a multicenter trial evaluating ranitidine in the treatment of gastroesophageal reflux disease, the therapeutic responses of patients with and without abnormal endoscopic findings were evaluated. All patients were randomized to either placebo or ranitidine (150 mg bid) treatment groups. The treatment interval was 6 wk. Thirty-seven percent of 283 patients enrolled in the trial had normal baseline endoscopy. Compared to the placebo group, 147 evaluable ranitidine patients with abnormal endoscopy displayed a marked and rapid symptom reduction which was sustained throughout the last 4 wk of therapy. Despite randomization of endoscopically normal patients, those treated with ranitidine had significantly more heartburn at baseline. However, the 89 evaluable ranitidine-treated patients with normal endoscopy also experienced a marked and rapid reduction in heartburn at the end of 1 wk. The symptomatic improvement in the endoscopically abnormal ranitidine patients was significantly greater (p less than 0.05) than that observed in the endoscopically normal ranitidine group. Since both groups fared better on ranitidine than placebo, the results of this study indicate that ranitidine is an effective treatment for patients with heartburn symptoms and documented esophageal acid sensitivity whether or not endoscopic parameters for esophagitis are present.