Previous clinical trials have evaluated a large number of symptomatic individuals with heartburn. Most studies have documented the need for multiple daily dosing with H2-antagonists to achieve clinical and statistical efficacy for symptom relief. The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens, 40 mg nocte and 20 mg b.d. with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis. Famotidine (20 mg) b.d. reduced and eventually completely relieved gastro-oesophageal reflux disease symptoms in most patients during the 6-week trial. Global assessment of improvement at 2 and 6 weeks indicated significantly greater improvement with a b.d. treatment regimen than with either a 40 mg nocte or placebo treatment. No statistically significant differences between famotidine and placebo in the number of patients who experienced clinical adverse experiences were noted and no serious adverse events attributable to famotidine occurred. Based upon these findings, patients with gastro-oesophageal reflux symptoms experience good relief of their complaints with twice daily famotidine in standard doses.