The development of tests for variant Creutzfeldt-Jakob disease in the context of blood transfusion is technically complicated by a number of factors, including the long asymptomatic period and uncertainty as to whether infectivity is present in human blood at all. The specific needs of a donor test impose constraints. It is argued that the only possible analyte will be blood, and that while the initial work will involve animal studies, these will provide only an approximate guide. A rapid infectivity assay is key to confirming positives in human samples, and dilutions of infected human brain will probably provide adequate routine control samples to ensure the correct performance of the test.