In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.