Twelve American Indian nuclear families with 2-5 siblings have been HLA-D typed using mixed lymphocyte cultures and clusters of homozygous typing cells (HTC) of Caucasoid origin to detect DW1-DW7 and typing cells of American Indian origin to detect LD5A, LD15A and LD15B antigens. Results obtained demonstrate complete absence of DW1-DW7 in these families and illustrate the inheritance and segregation of LD5A, LD15A and LD15B. DR typing results obtained with the 8th International Histocompatibility Workshop genetic set of antisera indicate inheritance in coupling of DR2 with LD5A, of DR6.2 (DR3+6, MT1 negative, MT2 positive) with LD15A, and of DRW8 with LD15B. The existence of MLC activating antigen(s) different to DW4, yet associated to DRW4 in this population is postulated. The D/DR relationship present in this American Indian isolate demonstrate once more that DR2 can be inherited in combination with an HLA-D antigen different to DW2, and that LD15A HTC define a second sub-cluster of the broad DW6 specificity group, which is inherited with DRW6.2 and BW62 antigens in the Warao population.