Galactocerebroside (Gc) is a major component of myelin in both the peripheral and central nervous systems. Although it is regarded as an important glycolipid hapten of myelin in rabbit experimental allergic neuritis (EAN), its role in human demyelinating diseases is not known. We studied three post-infectious encephalitis (PIE) patients related to Mycoplasma pneumoniae infection. All three of three patients with encephalitis and M. pneumoniae infection were positive for Gc antibodies (100%), while 25% of 32 M. pneumoniae-infected patients without neurological disease were positive, and 3.8% of 52 healthy controls. This indicates anti-Gc antibody is induced by M. pneumoniae infection. One of the PIE patients, who had extraordinary high titer antibody to Gc, showed an extensive, diffuse white matter demyelination and poor recovery. Since circulating anti-Gc antibody induces central nervous system demyelination in animals with elevated antibody titers and disruption of the blood-brain barrier, anti-Gc antibody may have an important function in the increased demyelination in PIE patients after M. pneumoniae infection.