Objective: To study the correlation of the methylation of the promoters of hMLH1 and hMSH2 with microsatellite instability (MSI) in the tissues of gastric carcinomas. Methods: A total of 68 sporadic cases of gastric carcinoma were studied. Ten specimens of normal gastric mucosa served as control. Methylation of hMLH1 and hMSH2 was observed with methylation-specific PCR, and MSI analyzed with PCR-based techniques. Results: No methylation of hMLH1 and hMSH2 was found in 10 specimens of normal gastric mucosa. Methylation of hMLH1 was detected in 11 cases (16. 2%) of gastric cancers and MSI in at least one locus was found in 17 cases (25%) of the 68 with aid of 5 microsatellite markers, in which eight were MSI-H (≥2loci showed instability), nine MSI-L (only one locus showed instability), and fifty-one were MSS (no instability at any marker). The frequency of methylation was significantly high in MSI-H (87.5%) than in MSI-L (11.1%) and MSS (5.9%). (P＜0. 01-0. 001) but there was no difference of methylation frequency between the cases with MSI-L and those with MSS. Conclusion: Methylation of hMLH1 promoter is involved to the MSI pathway but not to the loss of heterozygosity (LOH) pathway in gastric carcinogenesis.