We determined the DNA sequence of the enzymatically amplified second exon of the DRB1 gene of the Drw12 haplotypes derived from three Japanese donors and found two distinct subtypes of the DRw12 haplotype. The two subtypes, designated DRw12a and DRw12b, had single-base substitutions that predicted one amino acid change at residue number 67. The sequence of the DRw12a and DRw12b subtypes differed from those of the other DR haplotypes, but in the first hypervariable region of the DRB1 gene the sequences were identical to those of the DRw8(Dw8.1) and DRw8(Dw8.3) haplotypes. The DRw12a and DRw12b subtypes were detected in a wide range of Japanese donors by genotyping with sequence-specific oligonucleotide probes synthesized according to the DNA sequences of the two subtypes. Results of this study demonstrated that the DRw12 haplotypes in the Japanese population are genetically diverse, as many other DR haplotypes are.