Glutamate neurotoxicity may be an underlying pathological mechanism contributing to neuronal cell loss in a variety of conditions including Alzheimer's disease (AD). In this study, we examined whether the β-amyloid protein found in the neuritic plaques of AD alters the susceptibility of neurons to excitotoxic damage. While mature cortical neurons exposed to β-amyloid protein for 2-4 days did not appear to be damaged, their vulnerability to low-intesity exposure to glutamate, N-methyl-d-aspartate, and kainate increased, suggesting that this mechanism may contribute to the neurodegeneration seen in AD. © 1990.