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Human T-lymphotropic virus type II (HTLV-II) is endemic among Amerindian tribes and is also prevalent at high levels among certain U.S. and European intravenous drug users (IVDU), and at lower levels among blood donors. Most epidemiologic evidence supports transmission via parenteral, breast-feeding, and sexual routes, although more quantitative studies of the latter two routes are needed. There is growing evidence that HTLV-II causes a neurologic syndrome similar to HTLV-I-associated myelopathy, but there is some controversy as to whether the clinical features of this illness differ between HTLV-II and HTLV-I cases. Preliminary evidence also suggests that HTLV-II may predispose to skin and soft tissue bacterial infections among IVDU. Questions amenable to future research are discussed.