The relationship between genotypes of HLA-DRB 1 alleles and the progression of bone destruction of RA patients was assessed. The genotypes of the HLA-DRB 1 alleles were determined in 329 Japanese patients with seropositive RNA by polymerase chain reaction and allele-specific oligonucleotide probe techniques. We regarded HLA-DRB 1* 0101, 0401, 0404, 0405, 1001 and 1402 as susceptible alleles of RA and classified the patients into three groups. The s/s group consisted of those with susceptible factors in both of the HLA-DRB 1 alleles. The s/n group was made up of those having one susceptible factor and one non-susceptible factor. The n/n group consisted of those possessing two non-susceptible factors. The grading of radiographic change that was evaluated by Larsen's criteria compared with the genotyped results. In the result, the median years taken to development to grade III, IV and V were significantly shorter in the s/s groups compared with that in the s/n and n/n groups. Thus, genotyping of HLA-DRB 1 can be a useful prognostic market in the progression of bone destruction of RA.