Since humoral factors have been implicated in the pathogenesis of multiple sclerosis (MS) and previous attempts at therapeutic intervention have not met with uniform success, plasma exchange (PE) was recently proposed for the management of this disease. We are currently investigating the possible effectiveness of PE in the treatment of MS, and to date 6 patients have been entered into the study. At least 4 of our patients who did not respond to conventional therapy have shown unequivocal, moderate to marked improvement following the first session of PE. At the time of treatment, these patients had an acute exacerbation of their disease. We found no correlation between clinical improvement and the serum immune complex levels, suggesting that other poorly known mechanisms were operative. Based on our preliminary results, we feel that PE may be efficacious in treating exacerbations of MS. More evidence is needed on the effects of PE in the chronic stage of the disease.