Immunohistochemical examination demonstrated widespread granular deposits of alpha -synuclein ( alpha SN) in the brains of sheep and goats with natural scrapie, especially in the cornu ammonis and subiculum of the hippocampus; this contrasted with the diffuse and non-granular immunolabelling seen in healthy controls. There was non-regular "co-localization" of PrPSc and alpha SN. The findings resembled those reported in Creutzfeldt-Jakob disease and in experimental prion disease in hamsters and mice. The results suggest that perturbation of alpha SN metabolism plays a role in human and animal prion diseases.