New highly-accurate stereological methods for estimating the total numbers of neurons in brain structures have been used to test for age-related neuron loss in the human hippocampal formation. Across the age range of 13 to 85 years, there was a substantial loss of neurons in the subiculum (52%) and in the hilus of the dentate gyrus (31%); the three remaining hippocampal subdivisions showed no significant change. These losses qualify as potential morphological correlates of senescent decline in relational memory in that they can be expected to compromise the functional integrity of a region of the brain known to be intimately involved in this type of memory. The regional pattern of neuron loss is similar in certain respects to the patterns of cell loss seen during the initial phases of ischemia and epilepsy and is fundamentally different from the pattern associated with Alzheimer's disease.