Identification of the aetiology of central nervous system infections requires the detection of either the organism or a microbe-specific immune response within the brain or cerebrospinal fluid. We describe a screening assay to detect herpes simplex virus, varicella zoster virus, cytomegalovirus, measles and Toxoplasma gondii specific antibodies in cerebrospinal fluid. Antigen-specific immunoblotting of oligoclonal IgG and IgM was used to confirm the presence of antibody. Of 51 consecutive cerebrospinal fluid samples received by the laboratory from patients with suspected central nervous system infection 18 (35%) were screen positive for one or more antigen. In only 7 of these were antigen-specific oligoclonal IgG or IgM bands confirmed. The assay provides a simple, cheap assay to screen for microbial-specific antibody in the cerebrospinal fluid samples of patients with suspected neurological infections.