In 1999, the UK implemented universal leucoreduction as a precaution against transmission of variant Creutzfeldt-Jakob disease by transfusion of domestic blood or red blood cells. We aimed to assess how effectively leucoreduction reduced infectivity of transmissible spongiform encephalopathies (TSEs) in blood. 450 mL of whole blood collected and pooled from scrapie-infected hamsters was leucoreduced with a commercial filter. Blood cell concentrations were quantified, and infectivity titres measured. Blood cell recovery and white blood cell removal complied with American Association of Blood Banks standards. Leucofiltration removed 42% (SD 12) of the total TSE infectivity in endogenously infected blood. Leucoreduction is necessary for the removal of white-cell-associated TSE infectivity from blood; however, it is not, by itself, sufficient to remove all blood-borne TSE infectivity.