The epidemic of bovine spongiform encephalopathy in the United Kingdom and the recognition of a variant of Creutzfeldt-Jakob disease prompted revision of the guidelines for slaughter of cattle and sheep to prevent contamination of the edible parts of the carcass with central nervous system tissue. We previously showed that captive bolt gun stunning, which is routinely used for the slaughter of cattle and sheep, causes entry of fragments of central nervous system tissue into the jugular vein. To determine whether such tissue can traverse pulmonary capillaries to enter the systemic circulation, we introduced small volumes of brain tissue that had been disrupted by stunning with a captive bolt gun into the jugular vein of sheep sent for slaughter. We examined aortic blood samples by immunocytochemistry for neurofilament and S100 proteins and by enzyme-linked immunosorbent assay for glial fibrillary acidic protein and found fragments of neurofilament- and S100-immunopositive central nervous system tissue in samples from 2 of 11 sheep and elevated glial fibrillary acidic protein in 6 sheep. Our findings suggest that central nervous system tissue that is dislodged during routine captive bolt gun stunning and slaughter of sheep can enter the systemic arterial circulation and that, in some cases, this method of slaughter of an animal infected with bovine spongiform encephalopathy would be likely to contaminate edible parts of the carcass with infective material.