The reasons for the development of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in certain infected individuals remain poorly understood, but the susceptibility should involve both viral factors and host conditions. To assess simultaneously both virus-induced activation of infected cells and the cellular response to virus producing cells, an analysis of fractionated peripheral blood lymphocytes obtained from patients with HAM/TSP (n = 15) were compared with those of asymptomatic HTLV-I carriers (n = 9) in an age-matched manner. The in vitro propagation of HTLV-I infection was evaluated as the spontaneous thymidine incorporation into CD4+ cells, and proliferative response of CD8+ cells against cultured and irradiated autologous CD4+ cells was employed to analyze the HTLV-I-induced cellular response. The comparative analysis using these two parameters demonstrated that HAM/TSP patients were characterized by the concomitance of a high inducibility of HTLV-I propagation and a high cellular responsiveness against HTLV-I as compared with asymptomatic HTLV-I carriers, suggesting the involvement of both of these factors in disease susceptibility. In addition, the coupled evaluation of these two in vitro phenomena may offer a better diagnostic hallmark for HTLV-I seropositive myelopathy cases with other known cause of myelopathy.