Lyme disease is said to produce a late syndrome resembling multiple sclerosis. We analyzed serum antibodies to Borrelia burgdorferi in 100 patients referred for possible MS. All lived in an area endemic for Lyme disease. Only 1 of 89 definite MS patients and 2 of 11 non-MS patients were antibody positive. Infection with Borrelia burgdorferi is rare in MS, and Lyme disease is unlikely to play a significant role in the differential diagnosis of MS.