The DPα-β heterodimers, like other HLA class II antigens (DR and DQ), blind to foreign or self antigenic peptides and specify heterodimeric glycoproteins involved in the regulation of the immune response. In this study, a comprehensive HAL-DPB1 genotyping method using PCR-RFLP instead of serological typing method were developed. Second exon of DPB1 was selectively amplified from genomic DNAs of 18 homozygous B-cell lines and lymphocytes of 100 unrelated Korean. Amplified DNA was digested with five allele specific restriction enzymes- EcoNI, RsaI, FokI, DdeI and SduI. And additional two restriction enzymes, BbvI and BssXI were used for the determination of two types, DPB1*0401/2201 and DPB1*0201/0501. DPB1*0501(f=0.30) was most frequently found among thirteen DPB1 alleles. DPB1*0401 (f=0.23), DPB1*0201 (f=0.15) and DPB1*0202 (f=0.085) alleles were also frequently determined among Koreans. This study shows that the PCR-RFLP is a relatively simple, fast and practical tool for the determination of HLA-DPB1 alleles. Moreover the population genetic study of HLA-DPB1 locus in Korean might be useful for disease association, individual identification and transplantation immunity.