We studied the susceptibility of B cell-deficient mice to encephalomyelitis following intraperitoneal inoculation of HSV-1. B cell-deficient mice developed striking CNS signs including tail atony, clumsy gait and limb paralysis after HSV-1 infection. In addition, B cell-deficient mice had decreased survival (LD50 = 2.2 x 10(7) PFU) compared to control C57BL/6 mice (LD50 = 2.3 x 10(8) PFU). B cell-deficient mice had encephalomyelitis and detectable virus in the brain 7 days post-infection while C57BL/6 mice did not. Passive transfer of hyperimmune sera protected B cell-deficient mice from death, suggesting a role for antibody in susceptibility to HSV-1 encephalomyelitis.