In a double-blind study comparing ranitidine to placebo in the treatment of symptomatic gastroesophageal reflux disease (GERD), we assessed gastric emptying time, gastroesophageal reflux, and gastrin response to food. Mean half-time for gastric emptying, measured using 99mTc-sulfur colloid, was 109 minutes in GERD and 102 minutes in nine healthy asymptomatic controls. This difference was not significant, but one-third of GERD had emptying times of 2 S.D.s beyond the mean for the normal controls. The patients with GERD refluxed an average of 2.3% (0.1-10%) of the isotope in 120 minutes compared with only 0.2% (0.0-0.5%) in control subjects. Reflux scans and gastric emptying times did not change with healing of esophagitis or with symptomatic improvement from ranitidine and antacids. There was no relationship between the percentage of the test dose refluxed into the esophagus and the rate of gastric emptying. The mean fasting gastrin concentration in GERD, 133 +/- 12 pg/ml, was higher than in healthy controls, 93 +/- 10 pg/ml (p less than 0.01). After stimulation with a standard meal, the integrated gastrin response (IGR) was similar in controls and GERD patients, but IGR was significantly higher after 6 weeks therapy with ranitidine. These results suggest that: 1) gastric emptying time may be prolonged in some patients with GERD, 2) basal but not food-stimulated gastrin concentrations may be abnormal in GERD, 3) reflux scans have limited use in the investigation of GERD, and 4) ranitidine therapy is associated with an increase in food-stimulated gastrin concentrations.