We examined CSF for Borrelia burgdorferi antigens using antigen-capture ELISA and Western (immuno) blot. Antigen-capture ELISA was positive in 38 of 77 (49%) CSF samples obtained from neurologic patients with presumed B burgdorferi infection, compared with one of 34 (3%) CSF samples obtained from other neurologic disease controls who came from a region endemic for Lyme disease. Western immunoblot was positive for B burgdorferi antigens in 12 of 22 (55%) CSF samples from the B burgdorferi infected groups, compared with none of 11 CSF samples from the control group. CSF antigen detection should prove helpful in evaluating patients for suspected neurologic Lyme disease.