Massive abnormalities of parvalbumin-immunoreactive cortical neurons were observed in the cerebral biopsy samples of 3 patients with Creutzfeldt-Jakob disease. Immunoreactive cells had reduced and short, often fragmented, dendrites, and large numbers of dendritic varicosities were observed. Since parvalbumin-immunoreactive neurons are the most important inhibitory cells in the cerebral cortex, the damage to these neurons may account, in part, for the impaired cortical function, and may play a role in the appearance of myoclonus and electroencephalographic patterns in patients with Creutzfeldt-Jakob disease.