The “modified host protein” model of scrapie proposes that the transmissible agent is composed of the degradation-resistant protein, Sp33–37, and that clinical and pathologic signs result from neurotoxic accumulations of this protein. Sp33–37 is an abnormal, amyloidogenic isoform of the normally occurring cellular protein Cp33–37. This study investigated the tissue distribution of Cp33–37 in hamster. In brain, Cp33–37 was most concentrated in the hippocampal formation. Immunohistochemical studies localized Cp33–37 to neurons and surrounding neuropil in hippocampus; septal, caudate, and thalamic nuclei; dorsal root ganglia cells; and large-diameter dorsal root axons. In non-neuronal hamster tissues, Cp33–37 was detected in circulating leukocytes, heart, skeletal muscle, lung, intestinal tract, spleen, testis, ovary, and some other organs. The presence of Cp33–37 in extracerebral tissues indicates that its function is not unique to brain. These results indicate that the molecular substrate for the production of Sp33–37, the scrapie agent, and scrapie amyloid is present in a variety of cerebral and extracerebral sites.