Autoantibodies against different axonal cytoskeletal proteins [the light (NFL) and medium (NFM) subunit of neurofilament and tubulin (TUB)] in serum and cerebrospinal fluid may be generated in response to the release of cytoskeleton from damaged neurons. We studied the relationships among these autoantibodies. Paired cerebrospinal fluid (CSF) and serum samples were obtained from 47 multiple sclerosis (MS) patients, 14 patients with neurodegenerative diseases, 21 patients with various neurological diseases and 16 normal control subjects. Levels of antibodies against NFL, NFM and TUB were related to each other in CSF in all groups, whereas close association of anti-cytoskeletal antibodies in serum was found in the MS group only. A concordant spectrum of anti-cytoskeletal antibodies is present in serum of MS patients, unlike in other neurological patients. The synergy between the spectrum of anti-cytoskeletal antibodies in serum and CSF might be one of the immunological features typical for the MS patients.