Iatrogenic transmission by blood transfusion has been described in cases of human variant Creutzfeldt-Jakob disease (vCJD), experimental ovine bovine spongiform encephalopathy (BSE), and natural sheep scrapie, demonstrating that blood in these prion diseases is infectious. However, the possible effect of the transfusion, derived from differences in the inoculum (blood) and the route of infection (intravenous), on the pathologic phenotype of the disease in the recipients is not known. This study describes the neuropathologic phenotype of PrP(d) accumulation in sheep succumbing to neurologic disease after blood transfusion from donors experimentally infected with BSE; these were either clinically or subclinically affected at the time of donation. We demonstrate that blood can become infectious at early stages of ovine BSE infection and that the PrP(d) immunohistochemical phenotype is maintained after transfusion. This suggests that a change in the pathologic phenotype of vCJD would not be expected as a result of exposure to infected blood.