Serological activity against several purified brain gangliosides has been demonstrated in sera of a proportion of multiple sclerosis patients, but not in normal individuals. The activity was determined by the capacity of the sera to bring about complement-dependent lysis of liposomes containing the respective ganglioside in their lipid bilayer. An apparent correlation is indicated between the severity of the disease and the extent of liposome lysis. Cerebrospinal fluid of the patients did not induce lysis, probably due to low antibody concentration.