Blood transfusion practices have resulted in iatrogenic cases of variant Creutzfeldt-Jakob disease (vCJD) and it is known that sheep blood is also infectious in the pre-clinical stages of natural scrapie and experimentally induced bovine spongiform encephalopathy (BSE). Further investigations have also shown that the pathological phenotype of sheep BSE and human vCJD is maintained after blood transfusion. The present study describes the pathological phenotype, in terms of accumulation of the disease-associated prion protein in brain and lymphoreticular tissues, in sheep receiving blood from donors infected with natural scrapie. The immunohistochemical examinations undertaken showed a degree of phenotypic variability within and between scrapie donors and recipients, which might be attributable to the presence of more than one scrapie strain amongst the donor sheep or to a host adaptation process, or to the interaction of both, rather than to the influence of the route of infection. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.