During the past few years, important progress has been made in the post-mortem diagnosis of transmissible spongiform encephalopathies (TSEs) (scrapie and BSE) due to the development of the so-called "rapid test" based on the immunological detection of the abnormal form of the prion protein (PrPres) in the central nervous system. These methods now allow routine and high throughput testing, opening the door to large-scale epidemiological studies and systematic testing at slaughterhouses, thus preventing the entry of contaminated carcasses into the human, food chain. It has been shown that some of these rapid tests allow pre-clinical diagnosis, anticipating by few months the appearance of clinical signs. In sheep and goat, PrPres can also be detected in peripheral lymphoid tissues a long time before the onset of clinical symptoms. As a consequence, the same rapid tests are suitable for pre-clinical diagnosis of scrapie in these species. It is very likely that the same kind of early diagnosis could be obtained for nuCJD. The real challenge in the field of TSE diagnosis is the establishment of a nuCJD test, conducted either on blood or urine, since these are the only biological fluids easily accessible from infected people. This is a very important issue to avoid iatrogenic transmission of nuCJD within the human population. This is also very difficult because the quantities of infectious agents in the blood are certainly 100-1000 times lower than those present in the brain. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.