Human T-lymphotropic virus type 1 (HTLV-1) is a persistent CD4 ⁺ T-lymphotropic retrovirus. Most HTLV-1-infected individuals remain asymptomatic, but a proportion develop adult T cell leukemia or inflammatory disease. It is not fully understood how HTLV-1 persists despite a strong immune response or what determines the risk of HTLV-1-associated diseases. Until recently, it has been difficult to quantify lymphocyte kinetics in humans in vivo . Here, we used deuterated glucose labeling to quantify in vivo lymphocyte dynamics in HTLV-1-infected individuals. We then used these results to address four questions. ( i ) What is the impact of HTLV-1 infection on lymphocyte dynamics? ( ii ) How does HTLV-1 persist? ( iii ) What is the extent of HTLV-1 expression in vivo ? ( iv ) What features of lymphocyte kinetics are associated with HTLV-1-associated myelopathy/tropical spastic paraparesis? We found that CD4 ⁺ CD45RO ⁺ and CD8 ⁺ CD45RO ⁺ T lymphocyte proliferation was elevated in HTLV-1-infected subjects compared with controls, with an extra 10 ¹² lymphocytes produced per year in an HTLV-1-infected subject. The in vivo proliferation rate of CD4 ⁺ CD45RO ⁺ cells also correlated with ex vivo viral expression. Finally, the inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis was associated with significantly increased CD4 ⁺ CD45RO ⁺ cell proliferation. We suggest that there is persistent viral gene expression in vivo , which is necessary for the maintenance of the proviral load and determines HTLV-1-associated myelopathy/tropical spastic paraparesis risk.