Objective: To obtain further information on the epidemology of Helicobacter pylori in man, including the pattern of H. pylori distribution in human gastric mucosa and its relationship to chronic atrophic gastritis. Methods: Phenol red dye spraying endoscopy was performed in 74 patients with chronic gastritis, to determine the distribution of H. pylori in human gastric mucosa in vivo. To clarify the relationship between the presence of H. pylori and the red color reaction, two biopsy specimens each were taken from areas showing and not showing the red color changes, for histological and bacteriological studies. Results: Glandular atrophy was classified according to three histological groups, none, slight and severe with intestinal metaplasia. In the groups with no glandular atrophy, H. pylori was found in two (11.8%) out of 17 patients, both showing diffuse staining. In the group with slight glandular atrophy, 35 (72.9%) out of 48 patients showed diffuse staining. In contrast, in the group with severe glandular atrophy, only three patients (33.3%) showed the red color reaction. These results show that the frequency of red color changes decreased with progressive glandular atrophy and accompanying intestinal metaplasia. In addition, 45 patients, 29 H. pylori-infected and 16 uninfected, were followed endoscopically for up to 8 years. Eighteen (62.1%) of the H. pylori-infected patients showed a cephalad shift in the fundic-pyloric border, compared with only one (6.3%) of the uninfected patients. The histological findings of glandular atrophy remained unchanged in the uninfected patients, but glandular atrophy progressed in nine (31.0%) of the 29 infected patients. Conclusions: Continued infection with H. pylori is likely to lead to glandular atrophy in human gastric mucosa, and to cause a cephalad shift in the fundic-pyloric border.