Immunocytochemistry was used to examine MAP5 immunoreactivity in the hippocampal formation obtained postmortem from five elderly, normal individuals, six individuals with Alzheimer's disease (AD), and two "transition" cases that did not have a history of dementia but did exhibit significant AD pathology. In all of the cases examined, axonal staining was restricted to the mossy fibers and their terminal field in CA3 stratum lucidum. In control cases, MAP5 immunoreactivity was observed in the neuronal cytoplasm and the proximal portion of the apical dendrites of pyramidal and granule cells. In both AD and transition cases, increased intensity of immunostaining was observed in CA3 pyramidal, subicular, and dentate gyrus granule cell neurons. Within individual neurons, immunoreactivity filled the neuronal perikarya, including the nuclear region, and the apical dendrite. Punctate staining was observed in neuritic plaques, but neurofibrillary tangles and neuropil threads were not immunostained. The increase and altered distribution of MAP5 immunoreactivity in both vulnerable and nonvulnerable neurons in AD may reflect an aberrant sprouting response. The increased expression of early cytoskeletal proteins may be tolerated in some regions such as CA3, but not in others including CA1 where the increased expression appear to precede aberrant phosphorylation, proteolysis, and incorporation of cytoskeletal proteins into AD pathology. Alternatively, the results could reflect sprouting in response to the neuronal loss and degeneration.