Phage displayed random peptide libraries were screened in order to identify phagotopes reacting with the IgG present in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Six families of phagotopes each composed of different isolates were identified. These phagotopes were used as reagents, to characterise IgG present in the CSF of MS patients. The following results were obtained: (a) CSF antibodies from different patients display different specificities; (b) anti-phagotope antibodies are also present in the serum of MS patients; (c) Anti-phagotope antibodies are equally frequent in the serum of MS patients and of healthy individuals; (d) some of the anti-phagotope antibodies are enriched in the CSF of MS patients. These data show that the natural antigen(s) recognised by CSF antibodies is rather common in the general population. By using the selected phagotopes as immunogens in rabbits, we have derived large quantities of anti-phagotope antisera which can provide for useful tools toward the identification of the natural antigen(s) recognised by MS CSF antibodies.