Medial temporal lobe (MTL) atrophy is an important marker for the clinical diagnosis of Alzheimer's disease at its prodromal stages. Several brain lesions have been associated with MTL atrophy including hippocampal sclerosis, neurodegenerative neuronal loss, and vascular pathology. To better explore the relationship between MTL volume on MRI and age-related degenerative and microvascular hippocampal pathology, we compared MTL volume on postmortem whole brain MRI and stereological estimates of the total number of neurons, cortical microinfarcts (CMIs), and neurofibrillary tangles (NFTs) in a consecutive autopsy series of 21 older individuals (11 females and 10 males, mean age 83.3 ± 5.8; range: 74-93 years, 7 demented and 14 nondemented). Our results revealed a very high percentage of cases with hippocampal CMIs (52%), particularly in the CA1 field. MTL volume was closely related to neuronal loss in both the CA1 area of the hippocampus (p = 0.0109) and the entorhinal cortex (p = 0.0272). MTL volume was not related to total CMI volume or to the total number of NFTs in our sample. In conclusion, hippocampal CMIs are very common in old age. MTL volume is determined essentially by the number of neurons in the hippocampus and does not appear to be related to the presence of NFTs or CMIs in this region.