Human T cell leukemia/lymphoma virus (HTLV-II) type II infection was detected by polymerase chain reaction or serologic analyses (or both) in 22% of 697 Indians of six different ethnic back-grounds inhabiting the Argentinean and Paraguayan Gran Chaco. None was infected with HTLV-I. The prevalence of HTLV-II increased with age (14% in those < 13 years and 23% in those > or = 13 years). HTLV-II infection was found in all 20 Gran Chaco communities studied, but marked differences (44%-4%) in the rate of infection were observed even in communities separated by only a few miles. These variations correlated closely with ethnicity. In the high-incidence communities, infection clustered within families, with evidence for both sexual and perinatal transmission, primarily via breast-feeding. By contrast, only 2% of 94 Mapuche Indians from southern Argentina were positive for HTLV-II. Analyses of pol and long terminal repeat sequences from 15 Gran Chaco HTLV-II strains indicated that they constitute a highly conserved branch of the HTLV-IIB substrain.