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Lyme disease, a tick-borne spirochetosis caused by Borrelia burgdorferi, produces protean neurologic manifestations, yet its neuropathogenesis is poorly understood. The affinity of the spirochete for cells of primary rat brain cultures and of the C6 glioma cell line was studied. B. burgdorferi adhered to both types of cells in a dose-dependent manner and exhibited an affinity for an extracellular matrix produced by the primary and by glioma cell cultures. Adherence of the spirochetes to the glial components of the primary brain culture could be an early event in the production of neurological injury; its affinity for cells could be the reason for its infrequent isolation from cerebrospinal fluid.