The pathogenesis of neurologic complications of Lassa fever is poorly understood. A Nigerian patient had fever, disorientation, seizures, and blood-brain barrier dysfunction, and Lassa virus was found in cerebrospinal fluid (CSF) but not in serum. The concentration of Lassa virus RNA in CSF corresponded to 1 x 10(3) pfu/mL, as determined by a quantitative real-time polymerase chain reaction assay. To characterize the Lassa virus in CSF, the 3.5-kb S RNA was sequenced. In the S RNA coding sequences, the CSF strain differed between 20% and 24.6% from all known prototype strains. These data suggest that Lassa virus or specific Lassa virus strains can persist in the central nervous system and thus contribute to neuropathogenesis. Lassa virus infection should be considered in West African patients or in travelers returning from this area who present only with fever and neurologic signs.