Brain and immune system tissues express myelin basic protein (MBP) mRNAs that contain novel exons upstream of those of the classic MBPs. We have generated antisera against a recombinant protein that includes the deduced sequence for one of the predicted species of the new MBP-related protein, hemopoietic HMBPR1. We report here the presence of multiple proteins reactive to the antisera in a range of tissues. The principal finding is that the antisera recognize a family of proteins of approximately 25 kDa that are restricted to brain, thymus, and spleen, the only tissues in which the new MBP-related transcripts are present. These antisera also detect other proteins of apparent molecular mass consistent with other isoforms of predicted MBP-related proteins. The expression of MBP-related proteins in immune system tissues may be important for self-tolerance to CNS MBPs and the initiation of immune-associated demyelinating diseases.