The neuropathological and biochemical features of the 89 histologically confirmed cases of variant Creutzfeldt-Jakob disease (vCJD) diagnosed up to the end of October 2001 in the UK are reviewed. Histology of the central nervous system, lymphoid tissues and other organs was accompanied by immunocytochemistry and Western blot analysis of the disease-associated form of the prion protein (PrP(RES)). All patients with vCJD were methionine homozygotes at codon 129 of the PrP gene. The pathology of vCJD showed relatively uniform morphological and immunocytochemical characteristics, which were distinct from other forms of CJD. PrP(RES) accumulation was widespread in lymphoid tissues in vCJD, but was not identified in other non-neural tissues. PrP(RES) in vCJD brain tissue showed a uniform glycotype pattern distinct from sporadic CJD. Given the increasingly widespread occurrence of bovine spongiform encephalopathy in Europe and Asia, there is a major need for widespread CJD surveillance. This should be accompanied by a multidisciplinary laboratory approach to the investigation and diagnosis of all forms of CJD, with the need to investigate autopsy tissues from suspected cases by the histological and biochemical techniques described herein.