Analyses of HLA-DRB1 gene using polymerase chain reaction and sequence-specific oligonucleotide probes reveal that the amino acid sequence Glu-Gln-Arg-Arg-Ala-Ala-Val at positions 69-75 of the third hypervariable region (HVR) of HLA-DR beta 1 chain is significantly associated with HTLV-I-associated myelopathy (HAM). Since the frequency of this sequence in HTLV-I carriers is almost the same as that in controls from Kagoshima (an endemic area of HTLV-I), this sequence may be related to susceptibility to HAM rather than to susceptibility to HTLV-I infection. Since this third HVR functions as putative antigen-binding sites and T cell recognition sites, the amino acid sequence of positions 68-73 was analyzed in detail. The analysis reveals that Gln70 and Arg71 are relevant to the occurrence of HAM.