Rabbits were immunized with white matter (WM) membrane fractions isolated from autopsy brain specimens of three patients with multiple sclerosis (MS), and three controls. All the rabbits developed high serum antibody titers to the MS and control WM fractions, as tested by enzyme immunoassay. Antibodies against WM membrane components were analyzed further by immunoprecipitation of radio-labeled WM proteins and subsequent polyacrylamide gradient gel electrophoresis. Antigenic membrane components with molecular weights of 138 000, 111 000, 86 500, 79 600, 69 000, 63 000, 58 000, 53 400, 45 700, 24 500 and 22 300 were found in both MS and control WM. Although there may have been some quantitative differences in these immunogenic proteins of MS and normal WM, no multiple sclerosis-specific membrane antigen could be demonstrated. The hyperimmune anti-WM sera did not precipitate 35S-labeled polypeptides from cells infected with herpes simplex type 1, adeno type 5, measles, mumps, rubella, respiratory syncytial, parainfluenza type 2 or cytomegaloviruses, which suggests that the MS brain WM membrane proteins do not share common antigenic determinants with the viral polypeptides.