We have recently shown that adaptation of gastric mucosa to aspirin (ASA) is disturbed in Helicobacter pylori (H. pylori)-infected human stomach, but can be restored by eradication of the bacterium. The aim of this study was 1) to evaluate the influence of H. pylori on expression of heat shock protein 70 (HSP70) during ASA ingestion in these subjects and in mice model and 2) to evaluate, whether altered HSP70 expression might be associated with different adaptation to ASA in H. pylori-positive and eradicated subjects. The gastric mucosal HSP 70 gene expression was determined by quantitative RT-PCR and Western blot and immunohistochemistry during 14 days of ASA ingestion (1 g bid) in the same 8 subjects before and 3 months after successful eradication of H. pylori. In addition, HSP70 mRNA and protein expression were examined in 30 mice without and with H. pylori infection and eradication. During 14 days of ASA treatment, human H. pylori-infected mucosa revealed a decrease of HSP70 expression, while after eradication a higher expression and further increase of HSP70 expression during ASA ingestion were observed. Mice inoculated with H. pylori also exhibited decreased gastric mucosal HSP70 mRNA expression that was restored after eradication therapy. Decreased basal and ASA-induced expression of HSP70 may partly be responsible for impaired gastric adaptation to ASA in H. pylori-positive subjects. We conclude that 1. The HSP70 gene and protein expression is reduced during infection with H. pylori in men and mice and that gastric adaptation to ASA in H. pylori eradicated subjects is accompanied by increased HSP70 expression; 2. It is reasonable to assume that decreased HSP70 expression might contribute to disturbed gastric adaptation in H. pylori infection in humans and 3. The expression of HSP70 plays an important role in the mechanism of gastric adaptation to ASA and that H. pylori infection interferes with this adaptation due to decrease of HSP70 expression in gastric mucosal cells.