Sodium-dependent glutamate binding was studied as a possible index of the integrity of glutamate/aspartate (Glu/Asp) nerve endings in seven cortical areas from postmortem brains of 15 persons with senile dementia of the Alzheimer type (SD), 10 controls matched for age, sex and postmortem delay (PMD), and single cases of Down's syndrome and Parkinson-dementia. Binding affinities (Kd) were quite variable from brain to brain but showed no relation to sex, age, PMD or disease. Specific binding site densities did not vary with age or sex but showed overall a significant negative correlation with PMD, a significant decrease in SD, and a significant correlation in the SD--but not the control--samples with choline acetyltransferase (ChAT) activities. The binding data on individual brain regions, however, showed no significant difference between SD cases and controls despite highly significant differences in the ChAT activities. The overall results support but do not confirm a defect in cortical Glu/Asp systems in SD. Reported and obtained data on lesioned rats are summarized to suggest that sodium-dependent glutamate binding may be an ineffective index of Glu/Asp nerve endings.