A prospective study was performed in 190 control subjects and in 236 patients with different degrees of endoscopic esophagitis in order to determine the prevalence of Helicobacter pylori infection at duodenal gastric and esophageal mucosa and its correlation with histological findings. All patients with pathologic gastroesophageal reflux had 24-h pH monitoring studies confirming the presence of acid reflux into the esophagus. Besides the endoscopic findings, biopsies were taken from the duodenal bulb, gastric antrum, gastric fundus and distal esophagus or at the specialized columnar epithelium in patients with Barrett's esophagus. Patients with pathological gastroesophageal reflux were divided into three groups: 55 with absence of endoscopic esophagitis (gastroesophageal reflux), 81 patients with erosive esophagitis and 100 patients with Barrett's esophagus. There was no H. pylori infection present at duodenal or esophageal mucosa or at the specialized columnar epithelium of the distal esophagus in any case. The prevalence of H. pylori infection at gastric antrum was similar in controls and in any group of patients with reflux disease (20-25% of H. pylori infection). No differences in age and sex distribution were seen. H. pylori infection at gastric fundus was very low (less than 5%). The presence of HP infections was correlated with the finding of chronic active superficial or athrophic gastritis while, in the absence of H. pylori infection, gastric mucosa was normal. In the presence of intestinal metaplasia, no H. pylori infection occurred. Based on these findings, it seems that there is no significant evidence for an important pathogenic role for H. pylori infection in the development of pathologic chronic gastroesophageal reflux, erosive esophagitis or Barrett's esophagus, and the presence of antral gastritis in patients with Barrett's esophagus is closely related to the presence of H. pylori infection, and probably not related to an increased duodenogastric reflux.