The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained.