In less than 1 % of persistently infected individuals, human T cell lymphotropic virus type I (HTLV-I) causes a chronic inflammatory disease of the central nervous system (CNS), called HTLV-I-associated myelopathy/tropical spastic paraparesis. Important prerequisites for disease induction are oligoclonal expansion of HTLV-I-infected CD4+ T lymphocytes, their trafficking across the blood-brain barrier, expression of viral proteins in the CNS, and an increased immune response within the CNS. The HTLV-I Taxi protein has unique abilities to transactivate viral and cellular genes in T lymphocytes, but possibly also in cells of the CNS. Thus Taxi supports the persistence of HTLV-I, the ongoing immune responses within the CNS and the destruction of myelin and axons, most pronounced in the thoracic spinal cord.