The recent emergence of variant Creutzfeldt-Jakob disease (vCJD) in the UK, and demonstration that vCJD is caused by the same prion strain that causes bovine spongiform encephalopathy, have led to concerns about the possibility of a human epidemic. Although only 79 cases of vCJD have occurred to date, it is likely that hundreds of thousands of infected cattle entered the human food chain in the late 1980s and early 1990s, and the average incubation period of vCJD is unknown. Mathematical models have not yet been able to give useful predictions of future numbers of cases, and in the absence of a blood test for vCJD, current attempts to reduce uncertainties about future numbers of cases are based on the accumulation of PrPSc in lymphoreticular tissues. Extensive lymphoreticular PrPSc accumulation has been seen in all cases of symptomatic vCJD so far examined, and in one case 8 months prior to the onset of symptoms. Animal models of prion disease suggest that lymphoreticular involvement occurs early in the incubation period and reliably predicts future neurological disease. Based on these data, large scale anonymous studies looking for PrP accumulation in surgically removed tonsillectomy and appendicectomy specimens are underway. Examination of the first 3000 specimens has not revealed any positive samples, but at the moment the significance of negative findings is uncertain. It is anticipated that by the time these studies are complete more data will be available on how early PrP can be demonstrated in lymphoreticular tissue in vCJD, which together with the results from examination of further samples, will allow some comment as to the likelihood of a large human vCJD epidemic.