The prion protein gene was studied in patients with definite or probable Creutzfeldt-Jakob disease (CJD) registered by national CJD units of 6 European countries. The role of genetic factors in CJD was also investigated by comparing the frequencies of a family history of dementia and Parkinson's disease in CJD cases and matched controls. Codon 129 genotype was examined in 337 CJD cases of whom 73.2 p. 100 were homozygous for methionine, 10.9 p. 100 were homozygous for valine and 15.7 p. 100 were heterozygous. The genotype frequencies were not statistically different across countries. Future differences, if any, would constitute a meaningful signal for the surveillance of CJD in Europe. A prion protein gene mutation was found in 14.5 p. 100 of CJD cases; only 40 p. 100 of them had a known family history of CJD. The case-control study showed that positive family histories of dementia and Parkinson's disease were both associated with CJD. Although recall bias is the most likely explanation for this finding, the hypothesis that neurodegenerative diseases might share unknown genetic risk factors can also be considered.