To investigate the HLA-linked disease-contorolling gene(s) for Buergers disease, we have genotyped 72 unrelated Japanese patients and 224 healthy controls for HLA-B, DRB 1 and MICA genes. It was revealed that the frequencies of HLA-B and DRB1 were significantly increased in the patients (B^* 5401;27.8% in the patients vs. 11.6% in the controls, OR=2.35,p=0.0.012, and DRB1 ^* 1501;31.9% vs. 9.4%, OR=4.53,pc＜0.0001), while the frequency of MICA 1.4 allele, which is in strong linkage disequibrium with HLA-B^* 5401 in the Japanese population, was not significantly deviated between the patients and controls. A comparison of odds ratio for the risk of disease conferred by HLA-B and DRB1^* 1501has suggested that these disease-associated alleles may be independent genetic risk factors of Buergers disease or that there might he at least 2 different etiologies; one is associated with HLA-B 1 and the other is associated with HLA-DRB1^* 1501. On the other hand, the frequency of MICA 1.2 allele was significantly decreased in the patients (30.6% vs. 48.2%, OR=0.47, pc=0.04). These observations suggest that both the susceptibility and resistance to Buergers disease are linked to BLA, hut they are controlled by different genes in the HLA region. The HLA system comprises a complex array of genes encoding for polymorphic cell surface glycoproteins that play fundmental roles in immune responses to foreign as well as self antigens and may control the susceptibility and/or resistance to various diseases including autoimmune diseases. There are two distinct types of HLA molecules; classI (HLA-A, B and C) and classII (HLA-DR, DQ and DP). The polymorphisms of the HLA molecules have been analyzed by serological typing system utilizing the complement-dependent cytotoxicity assay and panels of selected antisera. However, recent development of typing technology at the DNA level has revealed that there are many alleles which could not he distinguished by the serological typing (1). Therefore, the associations between HLA and certain diseases are now analyzed in more detail at the DNA level by using PCR-based DNA typing technologies (2). Buergers disease (thromboangiitis obliterans) is characterized by thrombotic obstruction of middle- and small-sized arteries with inflammation (3). Its etiology or pathogenesis remains unknown, although smoking is a known risk factor of the disease (4). On the other hand, the incidence of disease is more frequent in Asian countries than in European countries, suggesting that there are ethnic differences in the susceptibility and/or resistance to the disease (5). Because HLA shows ethnic differences in the allele frequencies and is involved in the inflammatory process, analysis of HLA may be important in understanding the pathogenesis of Buergers disease. In this respect, serological analysis of HLA in Buergers disease had been performed and it was reported that HLA-B54 and DR2 were associated with the disease in Japanese (6, 7), while no definite positive association between the disease and HLA was confirmed in Caucasians (8, 9). Because relatively small numbers of patients were analyzed in these serological studies, the association still remains to he confirmed. To investigate the association between HLA and Buergers disease in more precise way, we have analyzed polymorphisms of HLA-B, DRB 1 and MICA genes in the Japanese patients at the DNA level.