In this study we compared both endogenous gastrin release to a known gastrin stimulant, phenylalanine, and fasting antral mucosal gastrin concentration in normal subjects and patients with documented gastroesophageal reflux. Resting lower esophageal sphincter pressure in the reflux patients (14.7 +/- 1.5 mm Hg) was significantly less (p less than 0.01) than in the normal subjects (27.5 +/- 2.7 mm Hg). Basal serum gastrin concentrations were similar in the two groups. There were significant (p less than 0.05) increases in peak serum gastrin in response to intragastric administration of phenylalanine in both normal subjects (20.6 +/- 6.7 pg/ml, p less than 0.05) and refluxers (22.4 +/- 3.0 pg/ml, p less than 0.01) but there were no significant differences in these responses between normals and refluxers. Mean integrated gastrin response to phenylalanine in the reflux patients (812 +/- 116 pg ml-1 h-1) was slightly higher than that in normals (609 +/- 328 pg ml-1 h-1) although the difference was not significant. Antral gastrin concentration was slightly higher in reflux patients (15.7 +/- 2.2 ng/mg tissue) than in normals (10.4 +/- 4.2 ng/mg tissue), although this difference was not significant. There was no correlation between antral gastrin concentration and either integrated serum gastrin response or gastric acid output. We conclude that there is no difference between patients with gastroesophageal reflux and normal subjects with regard to serum gastrin levels, endogenous gastrin release, or antral gastrin concentration. These observations suggest no role for gastrin in the mediation of lower esophageal sphincter incompetence or the pathophysiology of gastroesophageal reflux.