Analysis of polymorphic systems, demonstrating differences among ethnic groups, provides a valuable tool for biology and medicine. Blast-1 is a member of the immunoglobulin superfamily and an activation-associated glycoprotein expressed on the surface of mononuclear cells. Blast-1 demonstrates DNA polymorphism in healthy controls and patients with rheumatoid arthritis (RA). The sizes of polymorphic restriction endonuclease fragments of genomic DNA encoding Blast-1 were 2.4 and 1.9 kb. In normal controls, the frequency of the homozygote for the 2.4 kb fragment (L-L) was 0.69 and 0.47, and that for the 1.9 kb fragment (S-S) was 0.04 and 0.11 in Caucasians and Japanese, respectively. The frequency of the heterozygote for both fragments (L-S) was 0.27 and 0.42 in Caucasians and Japanese, respectively. The frequencies of the L and S alleles were 0.83 and 0.17 for Caucasians, respectively, and were 0.68 and 0.32 for Japanese, respectively. The difference in the allele frequency between Caucasians and Japanese was significant. In Japanese patients with RA, the frequency of L-L, L-S and S-S types was 0.45, 0.45 and 0.10, respectively. Lung fibrosis in Japanese RA patients was associated with an increase in the L-S and S-S types and a decrease in the L-L type. The present study indicates that the investigation for gene polymorphisms of Blast-1 among distinct ethnic groups is important because Blast-1 appears to be a genetic marker for the manifestation associated with RA.