Mature cortical cultures, transiently deprived of glucose, developed slight neuronal damage that was exacerbated by exposure to a synthetic analog of the beta-amyloid protein deposited in the neuritic plaques of Alzheimer's disease. The non-competitive N-methyl-D-aspartate antagonist MK801 attenuated the injury-increasing effect of beta-amyloid protein implicating involvement of endogenous excitatory amino acids. These results suggest that beta-amyloid protein may accelerate neuronal degeneration in the presence of defective cerebral glucose metabolism which has been reported to occur in Alzheimer's disease.