Preimmune serum from a rabbit was found to contain antibodies that selectively immunostained myelin in brain sections of the rat. It also reacted with oligodendroglial cells in culture as shown by double labeling with galactocerebroside. On Western blots of two-dimensional electrophoretic gels of rat cortex, this antiserum recognized a 46 kD protein with a basic pI. The presence of this protein within myelin may help identify possible cellular mechanisms of myelination and the autoimmune serum might be useful in structural studies of myelin.