In inflammatory disease of the central nervous system (CNS), oligoclonal bands of immunoglobulin with restricted heterogeneity can often be observed in cerebrospinal fluid (CSF) samples. These antibodies can be directed against the disease inducing pathogen or might be autoreactive and involved in the process of brain inflammation and demyelination. We used a molecular biology approach to characterize these antibody responses in patients with Lyme disease. This disorder is caused by infections with the spirochete Borrelia burgdorferi which is transmitted by ticks. Lyme disease can be associated with neurological symptoms due to inflammation of the central and peripheral nervous system. Phage lambda gtll expression libraries from B. burgdorferi and human brain were screened with cerebrospinal fluid antibody probes from patients with Lyme disease. We obtained recombinant phage clones encoding antigenic proteins from both B. burgdorferi and human CNS libraries. Thus, in this study two patients with chronic Lyme disease produced antibodies against recombinant B. burgdorferi as well as against CNS proteins, and the generation of this transient autoimmune response might be essential to the development of demyelinating disease.