The human leukocyte antigen (HLA) complex includes the most polymorphic genes in humans. More than 600 allelic variants have been described in different populations. The HLA-B locus has contributed the largest number of alleles. Although Native American populations display a restricted number of HLA-alleles, many novel HLA class I alleles have been identified in indigenous communities of Central and South America. We have studied 248 unrelated individuals from three tribes of North-East Argentina and one from South-West Brazil, as well as 80 related individuals from the Brazilian tribe. In the course of this work, we found 8 new B-locus alleles and 2 novel A-locus alleles in these populations. Here we report the nucleotide sequences of A*0219, A*0222, B*3519, B*3520, B*3521, B*3912, B*4009 and B*4803 and we show their relationship with similar alleles. The new alleles B*35092 and B*3518 have been described by us in a previous paper. The possible mechanisms that may have produced these alleles over evolutionary time are discussed.