Chronic inflammation may be associated with microsatellite instability (MSI). To test the hypothesis that MSI frequently occurs in gastric intestinal metaplasia, we examined gastric biopsies from 58 subjects from an area of high risk for gastric cancer. These were selected to have 2 types of intestinal metaplasia: complete (31 subjects) and incomplete or mixed-type (27 subjects). None of the subjects had gastric cancer, but 95% had chronic inflammation with Helicobacter pylori. We used laser capture microdissection to retrieve metaplastic glands to compare with lymphocytes microdissected from the adjacent gastric mucosae in the same subjects. We performed microsatellite analysis using 6 microsatellite loci, including BAT26. None of the cases were found to have reproducible MSI, and only 1 case showed loss of heterozygosity at 1 marker, D3S1067. To test the sensitivity of our assay, we mixed templates to produce bands of different mobility and found that we could detect an aberrant microsatellite pattern if only 2% of the DNA showed that pattern. Our results indicate that MSI is a rare event in intestinal metaplasia in subjects who do not have gastric cancer.