This review examines information on clinical, pathological and immunological events in the slowly progressive neurologic disorder associated with the human T lymphotropic virus type-I (HTLV-I) termed HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). The role of cellular immune responses to HTLV-I in patients with HAM/TSP and how these responses may be associated with the pathogenesis of this disorder will be discussed. While a number of immunologic responses have been shown to be abnormal in HAM/TSP patients, studies on HTLV-I specific cytotoxic T cell responses (CTL) will be specifically examined. By defining such antigen specific functional cellular host responses to HTLV-I we hope to better understand the underlying mechanisms that may be involved in the neuropathology of HTLV-I associated neurologic disease. This has led to a number of HTLV-I associated immunopathogenic models that may be operative in HAM/TSP patients. Importantly, based on these models, potential immunotherapeutic strategies for disease intervention can be devised. Moreover, such an analysis may have significant implications for our understanding of other HTLV-I associated clinical disorders and other neurological diseases in which viral etiologies have been suggested.