Patients with noncardiac chest pain frequently have some evidence of gastroesophageal reflux. Yet there are few formal studies on the treatment of what appears to be reflux-related chest pain. The purpose of this study was to evaluate the effectiveness of intensive antireflux therapy in patients with noncardiac chest pain and gastroesophageal reflux and to determine whether patients who will respond to this therapy can be identified through routine esophageal testing. Thirteen patients with noncardiac chest pain and evidence of gastroesophageal reflux were treated with intensive antireflux therapy featuring high-dose ranitidine. Chest pain symptoms were scored from 0 (none) to 4 (severe) at entry into the study and at 8 weeks. Mean symptom scores were 2.9 +/- 0.3 at entry and 0.7 +/- 0.3 at 8 weeks. All patients had improvement, including those with a normal endoscopic or barium study (nine patients) and those for whom earlier standard antireflux therapy had failed (seven patients). Only one patient had a positive acid perfusion test, and only seven had any correlation of chest pain and reflux episodes during ambulatory monitoring. We concluded that many patients with noncardiac chest pain have gastroesophageal reflux, including those for whom an empiric trial of standard antireflux therapy fails. More aggressive antireflux therapy often leads to improvement in symptoms. Diagnostic studies requiring strict correlation of chest pain symptoms and reflux episodes are insensitive methods of determining which patients will respond to antireflux therapy.