In six of eight patients with chronic progressive multiple sclerosis (MS) who were previously unresponsive to corticosteroid medication, moderate but unequivocal improvement occurred after short-term plasmapheresis, prednisone, and azathioprine therapy. In four patients, improvement gradually disappeared in the 2 to 3 months after therapy, and two patients have remained improved. There were no exacerbations during the treatment period. No consistent improvement in evoked response batteries was seen after plasmapheresis; IgG levels in cerebrospinal fluid were lowered by plasmapheresis. A controlled trial to determine the efficacy of plasmapheresis in the treatment of MS is warranted.