We present six patients with acute fulminant episodes of CNS inflammatory demyelination who responded to therapeutic plasmapheresis after failing a course of high-dose methylprednisolone administered IV. Neurologic improvement occurred in three of the patients following the second plasmapheresis. Dramatic improvement in motor function (four patients) and language (two patients) began within 2 to 14 days and persisted during the 6 to 35 months (mean, 15 months) of follow-up. Results of this uncontrolled study suggest that plasmapheresis in the absence of other immunosuppressive drugs may have a role in the treatment of severe episodes of inflammatory demyelination in a select subset of MS patients.