Esophageal electrical potential difference (PD) was studied in 9 patients with symptomatic gastroesophageal reflux and in 9 healthy control subjects. None of the patients revealed gross mucosal damage by radiography or endoscopy, but all of them showed positive acid perfusion studies. In the stomach and across the lower esophageal sphincter PD profiles were remarkably similar in patients and controls. Throughout the lower esophagus however, PD values were slightly higher in patients with symptomatic reflux than in healthy volunteers. These data are in contrast to a previous investigation, in which patients with reflux-induced gross mucosal damage revealed a decreased PD in the lower esophagus. Thus it is concluded that PD measurements of the lower esophagus do not appear to be a valuable test in the differentiation of chest pain of cardiac and esophageal origin.