Abstract Thd investigate the genetic background of human T‐cell leukemia virus type I (HTLV‐I) and II (HTLV‐IIhd carriers among South American native Indians, we analyzed HLA DRBI*‐DQBI * haplotypes of the virus carriers from Andes highlands and Orinoco lowlands by the PCR‐RFLP genotyping method. It was revealed that the HTLV‐I‐carrying Andes natives had one of the 5 HLA haplotypes: DRBI*‐DQBI* 0403‐0302, 0802‐0402, 0901‐0303, 1406‐0302 and 0407‐0302, and that the Orinoco HTLV‐II carriers had one of the 3 HLA haplotypes: DRBI*‐DQBI* 1402‐0301, 1602‐0301 and 0404‐0302. The HLA haplotypes of Andes HTLV‐I carriers and Orinoco HTLV‐II carriers were mutually exclusive. The haplotypes associated with HTLV‐I carriers were commonly found among the Andes Indians and Japanese, which is the known HTLV‐I endemic population, while the haplotypes associated with HTLV‐II carriers were specifically found among the Orinoco Indians and North American Indians, among whom HTLV‐II is endemic. These reults suggested that HLA haplotypes might be ethnically segregated among South American natives and might be involved in the susceptibility to HTLV‐I and HTLV‐II infections.