In a search for possible central nervous system–specific autoantigens in multiple sclerosis (MS), a λ‐phage protein expression library was constructed from an oligodendrocyte‐precursor cell line. The library was screened with pooled cerebrospinal fluid (CSF) from 54 patients with definite MS according to the criteria of Poser. Pooled CSF samples from 44 patients with other neurological disease including bacterial meningitis and viral encephalitis were used as control. A total of 1,000,000 colonies were screened and 6 positive clones were detected. At the DNA level none of the sequences showed significant homology to a known coding sequence. All 6 clones contained an open reading frame for small peptides ranging from 14 to 38 amino acids. It was noteworthy that 5 clones contained a common sequence of 7 amino acids, which was highly homologous to a translated consensus Alu repeat epitope. Screening of sera and CSF from patients with MS showed that approximately 44% reacted with these so‐called Alu peptides, end‐point antibody titers in their sera ranging from 1:1,000 to 1:25,000. In addition, some samples selected by their reactivity with Alu peptides stained intensively the cytoplasm of oligodendrocyte precursors but not of astrocytes ex vivo. We postulate that autoantibodies to a hitherto unknown oligodendrocyte precursor‐derived B‐cell epitope could contribute to the pathogenesis in a subgroup of MS patients.