The hippocampal formations of 13 subjects with severe Alzheimer disease [AD; Global Deterioration Scale (GDS) stage 7] and of 5 age-matched subjects without symptoms of dementia were reconstructed from serial sections. Functional assessment staging (FAST) was used at the time of demise to assess 9 patients at stages 7a–c (incipient averbal and nonambulatory) and 4 patients at stages 7e–f (immobile). The duration of the disease from FAST stage 5 until demise ranged from 2 to 8 years in the first of these subgroups, and from 10 to 13 years in the second. The volumes of the entire hippocampal formation and of the cornu ammonis, its sectors and layers, the dentate gyrus, the subicular complex, and the entorhinal cortex were calculated. Hippocampal formation volume decreased by 36% in the incipient averbal and nonambulatory patients and by 60% in the severely functionally impaired immobile patients, in comparison with controls. In the final substages of AD, immobile patients exhibited significant atrophy, in comparison with controls, in the cornu ammonis and all of its sectors and layers except CA4, the subicular complex and all of its parts, and the entorhinal cortex (p < 0.05). Within the AD patient group, significant correlations were noted between both the magnitude of functional severity and the duration of AD and the volumes of most hippocampal formation subdivisions studied. For the cornu ammonis, subicular complex, and entorhinal cortex, volumetric loss correlations with FAST stage 7 ordinally enumerated substages were r = –0.71, –0.79, and –0.62, respectively. Calculations projected a decrease of 60% in the volume of the hippocampal formation over the duration of clinically manifest AD (from GDS and FAST stage 3 until demise). The projected decreases in the volumes of the cornu ammonis, subicular complex, and entorhinal cortex over the duration of AD were 64,70, and 51 %, respectively. We conclude that continuing changes occur in the hippocampal formation and most of its structural components throughout the clinical course of AD. These changes in the volume of the hippocampal subdivisions correlate with the stage and the duration of AD but not with age at onset of the disease.