Human T cell leukemia virus (HTLV) type II is endemic in certain American Indians, and high rates of infection occur in intravenous drug users (IVDUs). North American IVDUs are infected with two distinct variants, HTLV-IIa and -IIb. If IVDUs became infected as a result of interaction with members of an American Indian population, both viral forms should be demonstrable in such populations. Nucleotide sequence analysis of 630 bases of the env gene encoding the gp21 protein was done on DNA from 12 New Mexico Indians (8 Pueblo, 4 Navajo). All samples were typical subtype a or b viruses. Seven of the 8 Pueblo and 2 of 4 Navajo had subtype b; the rest had subtype a. The results are compatible with an indigenous New World origin for both subtypes of HTLV-II.