Focal involvement can be assumed in the initial stage of Creutzfeldt-Jakob disease (CJD). We correlated the clinical, electroencephalographic and neuropathological findings in 13 cases of CJD with special reference to focal or lateralized changes. Eight cases showed clinical and 9 electroencephalographic signs of asymmetry. Four cases with a course of the disease shorter than 12 months presented circumscribed tissue alterations at autopsy. Cases with a clinical duration longer than 12 months had pathological changes involving both hemispheres symmetrically. The infectious agent seems to spread through the entire brain within a period of 12 months.