Abstract A method for isolation of two multiple sclerosis(MS)-specific brain antigens  is described. The brain cytosol was passed through a Con A-Sepharose column and the glycoproteins containing MS-specific antigens (MSG) were eluted with 50 mmol/l methyl-α- d-glucopyranoside, pH 6. By fractionation of MSG on DEAE-cellulose, a fraction containing MS-specific antigens (MSG2) was eluted in 0.25 mol/l NaCl, after prior elution of other proteins with distilled water. The MS specific antigens in the MSG2 fraction were traced and characterized by crossed immunoelectrophoresis and isoelectric focusing. A quantitative determination of proteins eluted in MSG2 revealed that the 2 MS-specific antigens had been purified 10 000 times. Using this method to isolate the two MS-specific antigens of autopsy brains, they were found to be present in 7 7 MS brains and absent in 9 9 non-MS brains studied. The method described in the present communication may be used both for the partial purification of the MS-specific antigens as well as for the tracing of the specific antigens in different topographical areas of the MS brains.