Tropical spastic paraparesis is a neurological disorder that is most commonly seen in certain tropical (mainly Caribbean) areas and that presents as a progressive spastic paraparesis and urinary dysfunction. Recent studies have revealed an association between tropical spastic paraparesis and human T-cell lymphotropic virus type I (HTLV-I) infection. We report the results of a detailed morphological and immunocytochemical study of a patient with tropical spastic paraparesis. Lesions were restricted to the spinal cord and optic nerve, where demyelination, inflammation, and fiber loss were common features. Lymphocytes were seen closely applied to nerve fibers within which were changes resembling those seen in myelinated central nervous system cultures exposed to cytokines. Immunocytochemically, HTLV-I p19 core protein and a predominance of CD8+ (suppressor/cytotoxic) T cells and expression of class I major histocompatibility antigen were demonstrated in spinal cord lesions. It is postulated that cytotoxic T cells, either directly or via cytokines, induce lysis of the myelin sheath and subsequently the axon, resulting in a mixed picture of demyelination and axonal loss with secondary tractal degeneration. Despite this destruction, extensive remyelination was evident within affected areas of spinal cord.