We present 5 patients from two families with familial autosomal dominant diffuse Lewy body disease. All 5 patients initially showed parkinsonian symptoms that responded well to levodopa therapy; however, dementia followed and later progressed. In 3 patients, the disease was manifested before age 40 years, exhibiting wearing-off phenomenon and choreic limb dyskinesia. One patient was examined neuropathologically, and brain stem lesions compatible with Parkinson's disease were revealed, and Lewy bodies and senile plaques were found in the cerebral cortex. Familial cases of diffuse Lewy body disease may provide some explanation of the pathogenesis of this disease.