Sixty cases of Creutzfeldt-Jakob disease reported from 902 neurological clinics throughout Japan between 1975 and 1977 were examined in a retrospective case control study. Histories were obtained from patients, sex-matched neighbors, and spouses. No association was observed in either sex with five socioeconomic variables; exposures to eight species of animals; ingestion of raw meat or quadruped brains; eighteen diseases, allergies or immunizations; tooth extraction; blood transfusion; or lumbar puncture. Surgical operations within five years before disease onset were reported for 25.9% and 7.8% of male patients and pooled controls and for 24.2% and 9.6% of female patients and controls. Mechanical injuries were observed for the same period in 33.3% and 9.8% of male patients and controls and in 18.2% and 13.5% of female patients and controls. The operations and mechanical injuries varied in all groups as to body parts affected and nature of the lesions. Physical injuries including operations may be a predisposing factor to the development of Creutzfeldt-Jakob disease.