The overactivity of glutamatergic neurons may underlie some neurodegenerative disorders, including Alzheimer's disease (AD). We explored the relationship between glutamatergic transmission and neurofibrillary tangle formation by measuring [3H]-D-aspartate binding activity and the proportion of neurons containing tangles within individual thalamic nuclei in five AD cases. Five elderly normal and five Parkinson's disease (PD) cases were used as controls. A highly significant correlation between [3H]-D-aspartate binding and tangle counts in Alzheimer's disease suggests that those thalamic nuclei which normally receive a relatively dense glutamatergic afferent input are predisposed to tangle formation. There were no significant differences in individual thalamic nuclear [3H]-D-aspartate binding between controls and the AD and PD groups.