Variant Creutzfeldt-Jakob disease (CJD) is thought to be caused by dietary or other exposure to bovine spongiform encephalopathy (BSE) prions. The prevalence of preclinical or subclinical prion infection in the UK is currently unknown. Since clinical variant CJD is uniformly associated with tonsillar prion infection, we screened 2000 anonymous surgical tonsillectomy specimens for disease-associated prion protein. Analysis by both high sensitivity immunoblotting and immunohistochemistry detected no positive cases. However, this negative result cannot provide reassurance that relevant community infection is unlikely because of the fairly small sample size, demographic and age-related factors, and unknown test sensitivity during the prolonged incubation period. Nevertheless, our findings establish a protocol for prevalence screening on a national scale.