Despite the fact that the association of Helicobacter pylori (H. pylori)with an increased risk of gastric cancer has been well documented, the exact mechanisms of this association have not been fully elucidated. The aim of the present prospective study was to contribute to the exploration of these mechanisms by studying the relationship between H. pylori infection and proliferating cell nuclear antigen (PCNA) immunostaining in endoscopic biopsies in gastric antrum. Furthermore, we examined the impact of H. pylorieradication on this relationship. We studied 28 H. pyloripositive patients and the results were compared with 22 endoscopically and histologically normal H. pylorinegative patients (control group) who were comparable to the H. pyloripositive group for age and sex. In addition all H. pyloripositive patients were examined before and after treatment aiming to eradicate H. pylori. In the H. pylori(+) patients the median PCNA index was 35 (range 8-58) and this was significantly higher than the respective number in the control group [5.5 (2 14), p<0.001]. In patients studied before and after successful eradication of H. pylori(n=10) the corresponding numbers were 35 (8-56) and 7 (4 13) (p<0.01) the latter not being significantly different from the control group of H. pylori(-)patients. On the contrary, in patients without successful H. pylori eradication (n=18) the PCNA indices before and after treatment were similar [35.5 (21-58) vs 31.5 (20-56)]. It is concluded that H. pyloriinfection alters the replication cycle of the gastric mucosa inducing hyperproliferation, which return towards normal after successful H. pylori eradication.