The types of HLA-A, -B and -DRB1 genes were studied in 146 Japanese patients with multiple sclerosis (MS) using polymerase chain reaction-sequence-specific oligonucleotide probe analysis. Fifty-seven patients who displayed selective clinical involvement of the optic nerve and spinal cord were classified as having Asian type MS. The other 89 patients had disseminated central nervous system involvement and were classified as having Western type MS. The frequency of HLA-B*5101 was increased in both types of MS patients compared with controls. The frequency of HLA-DRB1*1501 was increased in Western type MS and the frequency of HLA-DRB1*0802 was increased in Asian type MS compared to controls. After correction of P values, the association of Western type MS patients with HLA-DRB1*1501 was statistically significant (Pc=0.0003) whereas other HLA alleles showed no significant association. These results suggest that HLA class I (HLA-A and -B) alleles may not contribute to a strong susceptibility to MS in Japanese compared to HLA class II (HLA-DRB1) alleles.