We studied two cases of ataxic Creutzfeldt-Jakob disease. EEG, CT, evoked responses, and CSF were normal in one purely ataxic patient. Diagnosis was established by cerebellar biopsy. Autopsy demonstrated devastating spongiform changes in the cerebellum, basal ganglia, and thalamus with rare focal changes in cerebral cortex. In the second patient, late generalized changes developed with dementia. Diagnostic studies included abnormal visual evoked responses, CSF with abnormal oligoclonal bands and IgG, and subacute spongiform encephalopathy in frontal lobe biopsy. Early diagnosis is best established by biopsy of brain areas most likely to be involved on the basis of clinical neurologic findings.