In seven of eight patients with progressive multiple sclerosis subjected to long-term plasmapheresis in combination with azathioprine and pulsed prednisone therapy, we found modest improvement of neurologic function. There was no change in auditory and visual evoked responses or serum demyelinating activity. In six of seven patients, cerebrospinal fluid IgG content decreased. Three additional patients in acute, severe exacerbation refractory to prednisone therapy made a substantial recovery, which commenced with plasmapheresis therapy. In two of them, the onset of clinical improvement after plasmapheresis was corroborated by decreased latency or increased amplitude of somatosensory evoked potentials. These results suggest that blood-borne factors, possibly autoantibodies, may play a role in the pathogenesis of the disease. The lesions may be at least partially reversible with plasmapheresis therapy, but a controlled trial is necessary to confirm these preliminary findings.