The host encoded cellular prion protein (PrP(C)) is an N-linked glycoprotein tethered to the cell membrane by a glycophosphatidylinositol (GPI) anchor. Under certain conditions, PrP(C) can undergo conversion into a conformationally-altered isoform (PrP(Sc)) widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (TSEs). Understanding the tissue-specific expression of PrP(C) is crucial considering that cells expressing high levels of PrP(C) bear a risk for conversion and accumulation of PrP(Sc). In the present study, fifteen bovine somatic tissues were analyzed for PrP(C) expression by quantitative western blot and immunohistochemistry. Quantitative western blot analysis revealed highest expression of PrP(C) in cerebellum, obex and spinal cord. Intermediate levels were detected in thymus, intestine, nerve, heart and spleen, and lower levels in lung, muscle, kidney, lymph node, skin, pancreas and liver. Immunohistochemical analysis detected intense cellular-specific PrP(C) staining in neurons, thymocytes and lymphocytes. PrP(C) was also detected in the enteric wall, pancreatic islets of langerhans, myocardium, pulmonary alveolar sacs, renal glomeruli and dermal epithelial cells. This study demonstrated the quantitatively varied, wide-spread, tissue- and cell-specific expression pattern of PrP(C) in bovine somatic tissues. The importance of this study is to lay the foundation for understanding the tissue-specific expression of PrP(C) and to consider the potential participation of more bovine tissues in the transmission of BSE infection.