Complete abrogation of the inflammatory response by high-dose cytotoxic therapy at an early stage of MS, when the nervous system has not yet sustained irreparable damage may be successful at preventing the inexorable progression. Immunological and hematological reconstitution follows abrogation through bone marrow transplantation. The issues are complex, and many factors, including baseline disability, the timing of this intervention, the intensity of the immune ablation, and depletion of lymphocytes from the graft, are all likely to influence treatment outcome. This article describes the immune ablation regimen for treatment of patients with poor prognosis MS, as performed in the Canadian MS-BMT study.