The relative distributions of 480 DR2-related DR,DQ haplotypes have been determined in Australian Aborigines, Papua New Guinean Highlanders, coastal Melanesians, Micronesians, Polynesians, Javanese, and Southern and Northern Chinese. Using sequence-specific oligonucleotides (SSOs) for hybridization of polymerase chain reaction (PCR) products from DRB1, DRB5, DQA1, and DQB1 genes, 15 different DR2-related haplotypes were identified. The predominant DR2 haplotype in Oceania involved a novel combination of DRB1*1502, DRB5*0101 alleles; this haplotype occurred sporadically in Java, but not in China. In Southern China, the most frequent DR2 haplotype involved the unusual arrangement DRB1*1602,DRB5*0101; alternatively, DRB1*1602 was associated with a new DRB5 SSO pattern. This study has important implications for molecular HLA-typing protocols that assume particular DRB1, DRB5 or DR,DQ linkage relationships. Further, the novel DRB1, DRB5 haplotype in Oceania suggests that the mixed lymphocyte culture (MLC) determinants Dw2 and Dw12 are discriminated by codon 86 at the DRB1 locus.