Using HLA-DW8 homozygous typing cells (HTC) of different ethnic origin it is possible to identify three subgroups of the DW8/DRW8 product (Mickelson et al., 1983). To further characterize the DW8.2 subgroup defined by HTCs of Amerindian origin we have now generated bulk PLTs within members of one extended Amerindian family and within selected HTCs of Caucasian, Oriental, and Amerindian origin. A panel of 61 DRW8 positive and negative donors of the three ethnic groups was used to test 15 different PLTs. Our results demonstrate that it is possible to generate DW8.1, 8.2, or 8.3 sensitized lymphocytes which distinguish in secondary cultures between each of the three subgroups of the DW8/DRW8 products. Of 40 DRW8 cells tested, 100% Caucasians typed as DW8.1, 100% Amerindians were 8.2; 75% Orientals were DW8.3; 8.3% were DW8.2, and 16.6% could not be classified within any of these subgroups. DRW8 individuals of mixed ethnic origin typed as either DW8.1 or DW8.2 and one DRW8 homozygous donor behaved as heterozygous 8.1/8.2. These results confirm the subdivision of the DW8/DRW8 product and explain the poor correlation and unexpected responses reported in MLC with DW8 HTCs and DRW8 donors of different ethnic origin.