Gastric emptying has been reported to be delayed in a significant percentage of patients with gastroesophageal reflux. The rationale for the use of metoclopramide and bethanechol in gastroesophageal reflux has been based on their ability to stimulate lower esophageal sphincter pressure and enhance acid clearance mechanisms. In this study, we investigated the comparative efficacies of metoclopramide and bethanchol in improving the rate of gastric emptying in gastroesophageal reflux patients in whom delayed emptying was present. Gastric emptying studies used an isotope-labeled mixed solid-liquid meal. Thirteen reflux patients with delayed gastric emptying received metoclopramide, 10 mg intramuscularly, and subcutaneous bethanechol, 0.07 mg/kg, in a randomized single-blind fashion. Eleven additional reflux patients with delayed gastric emptying received oral metoclopramide, 10 mg, in an open-labeled fashion. After parenteral metoclopramide, gastric emptying was significantly (p less than 0.05) faster compared with both the initial basal day and the bethanechol treatment day. Compared with the normal gastric emptying rate established in 26 control subjects, metoclopramide accelerated gastric emptying into the normal range. Bethanechol did not increase gastric emptying. Metoclopramide orally also significantly improved gastric emptying. Our study indicates that metoclopramide, both parenterally and orally, increased the rate of gastric emptying in those reflux esophagitis patients in whom it was delayed, while bethanechol did not improve the degree of gastric retention in the same patients. Our results extend the rationale for the therapeutic efficacy of metoclopramide in gastroesophageal reflux disease.