Down syndrome is caused by trisomy of chromosome 21 and is comprised of a constellation of abnormalities including neuropathological features that closely resemble those characterizing the neurodegeneration of Alzheimer disease. Because cultured cell lines from patients with Alzheimer disease and other neurodegenerations have a hypersensitivity to the lethal effects of DNA-damaging agents, we studied the response of Down syndrome lymphoblastoid lines to the lethal effects of ionizing and ultraviolet radiation. Lines from the four Down syndrome patients were more sensitive to X-rays than lines from 28 normal donors (P = 10(-4)), while survival of the Down syndrome lines after ultraviolet irradiation was not significantly different from normal. This hypersensitivity to X-rays, which may reflect defective repair of X-ray-induced DNA damage, represents the first abnormality common to cultured cells from both Down syndrome and Alzheimer disease patients.