Expression of human telomerase RNA (hTR) and telomerase activity in gastric cancer and corresponding non-cancerous mucosa were studied. Telomerase activity was detected in 23 (88%) of 26 carcinoma tissues. Although all tumor specimens and non-cancerous mucosa expressed various levels of hTR, 21 (81%) of 26 cases expressed hTR at a higher level in the tumor than that in the corresponding mucosa. All 8 gastric carcinoma cell lines also expressed hTR at high levels. Nine (35%) of 26 non-cancerous mucosa showed telomerase activity and all of them contained intestinal metaplasia. The incidence of telomerase-positive mucosa in grade 2 intestinal metaplasia was significantly higher than that in grade 0 or grade 1 intestinal metaplasia, whereas hTR overexpression was found in grade 0 or grade 1 intestinal metaplasia as well as grade 2 intestinal metaplasia. The degree of Helicobacter pylori infection increased in parallel with the level of hTR expression and telomerase positivity. These results overall suggest that Helicobacter pylori infection may be a strong trigger for hTR overexpression in intestinal metaplasia, and this may lead to telomerase reactivation.