Human major histocompatibility complex (HLA), located on 6p21.3, encodes for genes involved in antigen processing and presentation. Loss of heterozygosity (LOH) at 6p21.3 may cause downregulated expression of HLA, thus provide tumor cells with an immune-escape tumor phenotype. In the present study, we detected HLA class I expression in gastric cancer and correlated it with LOH at 6p21.3. The expression of HLA class I antigen was analyzed by immunohistochemical procedure in 50 fresh surgically removed gastric cancers and corresponding normal tissues using 5 monoclonal antibodies (mAbs). LOH studies were detected by using 6 microsatellite markers located at 6p21.3, 1 marker located at 6q21 and 2 microsatellite markers flanking the beta2m gene. HLA class I complex was obviously downregulated in gastric cancer compared with corresponding normal tissues (t=4.00, p<0.01). The expression of beta2m gene was also downregulated in tumor, but not concordant with HLA class I surface downregulation. Out of the 50 tumors, 25 (50%) showed LOH of at least one STR marker at 6p21.3 while only 11 (22%) showed LOH of the two markers flanking the beta2m gene. The LOH frequency of D6S105, which is close to HLA-A gene, was the highest in all STR markers studied (34%). Downregulation of HLA class I expression was correlated with loss of chromosomal regions at 6p21.3 (chi-squared = 5.13, p<0.05). Our results suggested that LOH of 6p21.3 contributed to HLA class I downregulated expression in gastric cancer especially at HLA-A locus. LOH of HLA-A gene might be one of the mechanisms underlying the abnormal expression of HLA class I complex.