To investigate the HLA-linked disease-controlling gene(s) for ulcerative colitis (UC), we have genotyped 94 unrelated Japanese patients with UC and 237 healthy controls for HLA-fl, DRB1 and HSP70-2 genes. The frequencies of HLA-B52 and DRB1* 1502 were significantly increased in the patients (B52; 56.4% in DC patients vs. 25.3% in the controls, OR-J.81, pc＜0.00001, and DRB1* l1502; 56.4% vs. 27.8%, OR=J.35, pc＜0.0001), while the frequency of HSP allele A was not significantly different between UC patients and controls. A comparison of odds ratio for the risk of disease conferred by HLA-B52 and DRB1* 1502 has suggested that HLA-1352 was a primary risk factor of UC. When DC patients were subdivided by HLA-B52, DRB1* 1502, and HSP70-2 allele A, HSP70-2 allele A was associated with younger onset of UC (p＜0.004) Although HLA-DRB1* 1502 and HLA-B52 are in strong linkage disequilibrium with the HSP70-2 allele A in Japanese population, neither HLA-DRB1* 1502 nor HLA-B52 was associated with unset age of UC. The association of HSP70-2 allele A with onset age of UC was observed even in the absence of HLA-B52 (p＜0.05), suggesting that the HSP70-2 allele A was primarily associated with onset age of UC independent of HLA-B52. These observations suggest that there are two loci in the HLA region, which may be involved in the pathogenesis of UC; the disease-susceptibility locus (HLA-B) and the unset age controlling locus (near HSP70-2).