Decreased lower esophageal sphincter pressure, transient relaxations of the lower esophageal sphincter, and acute increases in intra-abdominal pressure are among the most common pathogenic factors in gastroesophageal reflux. This study examines the effect of metoclopramide on these factors in patients with gastroesophageal reflux disease. Six patients with clinical and endoscopic evidence of esophagitis underwent esophageal manometry and intraesophageal pH monitoring over a 5-h period (1 h basal, and 4 h postprandially). The study was done on three different days: on day 1, after placebo, on day 2, after 10 mg po metoclopramide (order randomized), and on day 3, after metoclopramide 10 mg po quid for 7 days. Metoclopramide given for 1 wk significantly increased the basal lower esophageal sphincter pressure as compared to placebo and a single dose (p < 0.05). It also significantly decreased reflux episodes during the 3rd and 4th hour postprandially when given both as a single dose or after 1 wk of treatment. There was no significant difference in the other parameters measured. Repeated metoclopramide doses decrease reflux episodes in patients with reflux esophagitis by increasing basal lower esophageal sphincter pressure and possibly by accelerating gastric emptying.