We have previously reported that autologous HSCT using a cancer-specific myeloablative regimen (cyclophosphamide and total body irradiation) did not improve the neurologic disability (EDSS) score or even forestall progressive neurologic decline in patients with secondary progressive (axonal degenerative) multiple sclerosis. We, therefore, redesigned our approach to use a non-myeloablative regimen composed of agents specifically used to treat multiple sclerosis (cyclophosphamide and CAMPATH-1H) with infusion of cyclophosphamide / G-CSF mobilized autologous peripheral blood stem cells (PBSC) in patients with relapsing-remitting (inflammatory) multiple sclerosis. This regimen was designed for lymphoablation without myeloablation. Nineteen patients were treated. The regimen was well tolerated. No patient had either an early or late infectious events, 50% of patients never had a neutropenic fever. Of those who developed fever during transplant, fever lasted less than 24 hours and was related to CAMPATH-1H or stem cell infusion. One-half of the patients never required a RBC transfusion and one quarter never required a platelet transfusion. The mean day of WBC engraftment was day +8. The mean day of hospital discharge was day +10. CD4 recovery occurred by 6 months. The EDSS neurologic rating scale that varies from 0 (normal) to 10 (dead from neurologic disease) is evaluated every 6 months for 1 year then yearly. In fifteen patients with 6 or more months of follow-up, the EDSS has improved by at least one point in the majority (8 patients), remained unchanged in six and deteriorated in only one. A randomized multicenter trial, the Multiple Sclerosis International Stem Cell Transplant (MIST) trial comparing this approach to continued standard therapy for relapsing-remitting MS in patients with an enrollment EDSS of 2.0 to 6.0 is currently registering patients.