How does consumption of meat products infected with bovine spongiform encephalopathy (BSE) lead to development of Creutzfeldt-Jakob disease (CJD)? Studies of the brain, spleen and marrow of many immunodeficient mouse lines indicate that differentiated B lymphocytes are important for neuroinvasion. This discovery has implications for therapies against CJD, and also for the broader public-health issue of screening blood products against possible infection.