A national surveillance network for Creutzfeldt-Jakob disease (CJD) was established in France in the early 1990s with two objectives: to gain a better understanding of the incidence and risk factors associated with the various forms of this disease; to establish an early warning system capable of detecting the emergence of a form of CJD caused by the agent responsible for bovine spongiform encephalopathy (BSE). This network has been operational since 1992 and is integrated into the European surveillance network (EuroCJD), launched in 1993. Any suspected case of CJD is reported to the coordinating center, which investigates each case until a final clinical or neuropathological diagnosis is obtained. Reports come primarily from laboratories testing for the 14.3.3 protein in cerebrospinal fluid; the presence of this protein is one of the criteria for probable CJD. Suspected cases are defined using very broad criteria, prioritizing sensitivity over specificity; of the approximately 1,000 suspected cases reported to the network each year (1,062 in 2002), only about 12% are confirmed cases of CJD. The network collects biological material (DNA, serum, CSF, brains) according to standardized procedures. In France, between 1992 and 2002, 991 cases of CJD were identified (81.2% sporadic, 9.0% genetic, 9.2% iatrogenic, and 0.6% (N=6) vCJD caused by the BSE agent). Sporadic CJD is rare before age 50 and increases thereafter, peaking between ages 70 and 79 (mean age: 68.4 years; range 24–90). The annual incidence of sporadic CJD rose from 0.72 cases per million inhabitants in 1992 to 1.80 in 2002. This increase is observed only in individuals aged 60 and older and is particularly pronounced in the 80–89 age group. The frequency of the three genotypes (M-M, V-V, M-V) at codon 129 of the prion protein gene has varied over time: a steady decrease in sporadic MM cases and a parallel increase in V-V cases. The geographic distribution of sporadic CJD is statistically heterogeneous, and two small clusters of three cases each have been identified; no obvious link between the cases in each cluster has been identified. The network’s data and expertise have played an important role in public health decisions regarding human prion diseases. While the hypothesis of a major vCJD epidemic caused by the BSE agent can reasonably be ruled out, the persistence of major scientific uncertainties regarding this transmissible disease justifies maintaining an effective surveillance system for some time to come. (R.A.)