During the 15-year period 1968-1982, a total of 329 patients dying of Creutzfeldt-Jakob disease (CJD) were identified in continental France. Annual mortality rates stabilized at 0.5 to 0.6 cases per million (1.1 to 1.2 cases per million in Paris). Six percent of cases were familial. Although the frequency of CJD was related to population density, no contacts could be established among the great majority of patients. No association with socioeconomic factors, preceding trauma or surgery (excepting one iatrogenic neurosurgical case), or exposure to animal sources of infection was identified. Evidence from this and other epidemiologic studies suggests that CJD is a minimally contagious disease that may be principally acquired in early life from presymptomatic patients, asymptomatic carriers, or chance contamination by environmental sources. It is possible that CJD could also occur sporadically as a noncontagious disease by a mechanism akin to oncogenes in carcinogenesis.