To discern the T cell subtype associated with T cell differentiation, the expression of CD45RA and CD27 was measured from total CD8^high cells and from human T cell lymphotropic virus type I (HTLV-I) Tax11-19 peptide-specific CD8⁺ cells in peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phenotypically denned memory and/or effector cells (CD45RACD27⁺, CD45RA⁺CD27⁻, and CD45RA⁻ CD27) were increased in HAM/TSP CD8⁺ cells, compared with those of HTLV-1-seronegative healthy control subjects. The percentage of human leukocyte antigen (HLA)—DR—positive cells was also increased in CD8⁺ cells of HAM/TSP, compared with those in HLA-DR⁺CD8⁺ cells of healthy control subjects. HTLV-I provirus load correlated with the frequency of Taxll-19—specific CD8⁺ cells. The high frequency of memory and/or effector type HTLV-I Taxll-19—specific CD8⁺ cells suggests that continuous restimulation driven by HTLV-I antigens in vivo may be associated with the pathogenesis of HAM/TSP.