The clinical, neuropathological genetic and biochemical features of variant Creutzfeldt-Jakob disease (vCJD) are compared to the 926 other cases of suspected CJD referred to the National CJD Surveillance Unit laboratory from 1990-2001. Histological studies of the central nervous system, lymphoid tissues and other organs were accompanied by immunocytochemistry for prion protein (PrP); Western blot analysis of PrPRES was performed on frozen brain tissue. The pathology of vCJD showed relatively uniform morphological and immunocytochemical characteristics, with PrP accumulation in lymphoid tissues, but not in other non-neural tissues. PrPRES accumulation in vCJD showed a uniform glycotype pattern distinct from sporadic CJD. All cases of vCJD were methionine homozygotes at codon 129 of the PrP gene. In view of the spread of bovine spongiform encephalopathy in Europe and Japan, continuing surveillance is required for all forms of CJD, with histological and biochemical analysis of suspected cases to allow an accurate laboratory diagnosis.