The effects that human T cell leukemia virus (HTLV) type 1 and simian immunodeficiency virus (SIV) coinfection have on HTLV-1 dynamics and disease progression were tested in a nonhuman primate model. Seven rhesus macaques were experimentally inoculated with HTLV-1, and a persistent infection was established. Coinfection with SIV/smB670 resulted in increased HTLV-1 p19 antigens in peripheral blood mononuclear cells and HTLV-1 proviral loads. Circulating CD2+ and CD8+ T lymphocytes increased over preinoculation levels, along with a progressive decrease in CD4+ T cells, typical for terminal SIV disease. Finally documented was the striking emergence of up to 19% of HTLV-associated “flower cell” lymphocytes in the circulation, as seen in patients with adult T cell leukemia/lymphoma. CD8+CD25+ T cell subpopulation increases were positively correlated with flower cell appearance and suggested their possible role in this process. We conclude that SIV may have the potential to up-regulate HTLV-1 and disease expression.