The case of a 66-year-old woman with atypical Creutzfeldt-Jacob disease (CJD) presents several peculiarities. Pathologic examination confirmed a rare CJD case with primary generalized spongiform changes of the white matter and only moderate, but typical changes of the gray matter. Besides an essentially typical clinical course, the patient developed temporary diplopia and vertical eye movement paralysis. Intoxication had been excluded. Isoelectric focusing revealed oligoclonal CSF-IgG. Magnetic resonance imaging studies showed periventricular accentuated flat and striped hyperintense structures. EEG had CJD-typical periodic 1/s synchronous discharges. This case illustrates for the first time that in panencephalopathic type of CJD the cerebral white matter can be involved primarily and more extensively than the gray matter.