We compared the density of neurofibrillary tangles (NT) and neuritic (senile) plaques (NP) in 10 cortical areas, the amygdala, the hippocampus, the parahippocampal gyrus, and the cerebellum in patients with familial (FAD) and sporadic (SAD) Alzheimer's disease with early (< 55 years), intermediate (55-70 years) and late (> 70 years) ages of onset of dementia and age-matched controls. From a total of 199 cases of pathologically confirmed AD in our laboratory, 60 cases with appropriate brain sections and information as to family history, age of onset, duration of dementia, and brain weight were available for semiquantitative analysis of the frequency of NT and NP utilizing the Consortium to Establish a Registry for Alzheimer's Disease protocol. There were 28 SAD and 32 FAD (including seven Volga Germans) cases and 16 age-matched controls. In all brain regions, cases had more severe changes than controls (p < 0.001). Brain weight correlated inversely with duration of disease (p < 0.001). No significant differences were found in the severity scores of NT and NP between FAD and SAD. There was an inverse correlation between age of onset of dementia and the density of NT and NP in all regions in FAD and SAD combined. P values for NT were in the frontal (superior-middle and orbital, p < 0.0005; gyrus rectus, p = 0.0029), parietal (p = 0.0007), and medial occipital cortex (areas 17 and 18, p < 0.01), and for NP were in the superior temporal gyrus (p = 0.0085) and area 17 (p = 0.0003), and age of onset of dementia. In summary, using these criteria we found no compelling evidence that the neuropathologic characteristics of FAD are different from those of SAD.