Endemic infection with the human T cell leukemia/lymphoma viruses I and II (HTLV-I/II) is now recognized to be worldwide, and is becoming epidemic among intravenous drug abusers (IVDAs) in the United States and Europe. The number of people around the world infected with HTLV-I can be estimated as between 10 and 20 million (Table 1). HTLV-I causes a rapidly progressing adult T cell leukemia/lymphoma (ATLL), and an incurable progressive neuromyelopathy named tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), as well as a number of less well-studied syndromes. There is evidence that coinfection with HTLV-I or -II accelerates progression to AIDS. The cumulative lifetime risk of developing ATLL or TSP/HAM is around 5%, which, in terms of the induction of serious diseases, places HTLV-I in the same category of viruses for which efficient vaccines are made and used. Furthermore, there are factors favoring the feasibility of a vaccine against HTLV-I, in that the virus displays relatively low antigenic variability, natural immunity occurs in humans, and experimental vaccination with the envelope (Env) antigen is successful in animal models. A vaccine against HTLV-I would be of significant public health value in the fields of oncology, neurology, and AIDS, and it would serve as a pathfinder for a vaccine against HIV.