Synthesis of B cell-stimulating factor-2 (BSF-2) and IFN-gamma was shown in cerebrospinal fluids (CSF) collected from mice with experimental viral meningitis. In the CSF, the level of BSF-2 started to increase 24 h after intracerebral infection with lymphocytic choriomeningitis virus (LCMV) with rapid increase after day 4. IFN-gamma was not detected in the CSF before day 5 or 6 after infection, but increased sharply thereafter. In athymic nude mice, LCMV infection did not result in meningitis, and both BSF-2 and IFN-gamma levels were only slightly and transiently elevated. These findings suggest that activated mature T cells are required for development of disease and production of both BSF-2 and IFN-gamma. As observed in mice, BSF-2 was also detected in 16 out of 19 CSF samples collected from patients with acute viral infections of the central nervous system (CNS). Intrathecal production of BSF-2 and IFN-gamma may be instrumental in local production of antiviral antibodies by B lymphocytes/plasma cells invading the CNS during viral CNS disease.