Cerebrospinal fluid (CSF) and serum samples of 47 patients with serologically proven neuroborreliosis were examined by Western blotting for antibodies to a crude extract of human cortex (CNS) comprising a multitude (> 40) of protein bands. Intrathecal synthesis of total immunoglobulins was determined by the Reiber formula and of autoantibodies to CNS proteins by enzyme-linked immunoassay (ELISA) and by Western blotting. Employing ELISA, intrathecal synthesis of autoantibodies (IgG, IgM and/or IgA) was demonstrated in 40 of 47 patients with neuroborreliosis (85%), in 5 of 40 with multiple sclerosis (12%), and in 22 of 40 with viral meningoencephalitis (55%). Of 40, 35 and 15 patients with neuroborreliosis and an intrathecal synthesis of total IgG, IgM or IgA, 20 revealed an intrathecal production of IgG antibodies (50%), 24 of IgM antibodies (68%) and 6 of IgA autoantiodies (40%) in the CSF. The specificity of autoantibodies differed greatly between most patients. Of 24 different CNS proteins which elicited an immune response in various patients, identities could be determined only for the myelin basic protein (5 of 40) and for the three neurofilament proteins (NF-68, NF-150, NF-200) (13 of 40 patients). In this limited number of patients no significant correlation between individual clinical symptoms and certain autoantiodies could be detected. The higher frequency of intrathecally produced autoantibodies in patients with neuroborreliosis is assumed to result from mitogenic rather than specific activation of autoreactive B-cell clones by Borrelia burgdorferi. The pathogenic relevance of these autoantibodies remains to be determined.