To investigate the long-term effects of Helicobacter pylori gastritis on the gastric mucosa, 13 wild Japanese monkeys (six H. pylori-infected and seven controls) were monitored for 5 years. Colonization with H. pylori, the presence of macroscopic and histological gastritis, pyloric glandular height, and epithelial cell kinetics were investigated, using Ki-67 immunostaining in the gastric mucosa. In the infected group, persistent colonization with H. pylori was demonstrated by culture and histopathologic examination. In this group, the gastritis scores were significantly higher than in controls. Simultaneously, a significant decrease in the height of antral glands and a significant increase in the length of Ki-67-positive cells between the highest and lowest cells were also demonstrated in the infected animals. These experimental results directly demonstrate the effect of H. pylori infection on the gastric mucosa and may explain the potential mechanism for its causal role in the chain of events leading to gastric carcinoma.