The incidence of Creutzfeldt-Jakob disease (CJD) in Switzerland increased two-fold in 2001, and figures from the first quarter of 2002 indicate that it continues to rise. Neither age at onset nor duration of disease were different from previous years. Genetic analysis of the 27 reported cases revealed only one disease-associated mutation in the prion gene. None of the recognised risk factors for acquired CJD were reported on the official notification forms. Glycotype profiling, histopathology, and immunohistochemistry indicate that none of the cases fulfilled the definition of variant CJD, which is thought to be caused by bovine prions. Several scenarios could account for the increase in CJD, including improved reporting, iatrogenic transmission, and transmission of a prion zoonosis.