The diagnosis of new variant Creutzfeldt-Jakob disease is dependent on the neuropathological examination of brain tissue following brain biopsy or autopsy. The characteristic neuropathological features are multiple 'florid' plaques in the cerebral and cerebellar cortex, spongiform change most marked in the basal ganglia, severe thalamic gliosis and marked accumulation of the disease-associated prion protein in diffuse or pericellular deposits in the cerebrum and cerebellum. These features allow distinction from cases of sporadic, familial and iatrogenic Creutzfeldt-Jakob disease in neuropathological terms, new variant Creutzfeldt-Jakob disease also differs from sporadic Creutzfeldt-Jakob disease in terms of prion protein accumulation in lymphoid tissue outside the central nervous system. This has given rise to the possibility that prion protein in new variant Creutzfeldt-Jakob disease might be transported to the brain by circulating lymphocytes in the blood. Experimental strain typing of new variant Creutzfeldt-Jakob disease has shown that the transmissible agent responsible for this disorder is identical to that identified in bovine spongiform encephalopathy, confirming the hypothesis that exposure to the bovine spongiform encephalopathy agent, presumably through the diet, is the cause of new variant Creutzfeldt-Jakob disease.