To test whether aging is associated with alterations in the balance of cytoskeletal constituents, the relative concentrations of tau isoforms and seven other structural proteins were compared in the brains of 3-25-month-old mice. A tau species of approx. 63 kDa was substantially increased in the older animals while the levels of ankyrin, talin, spectrin, and actin were differentially decreased. The decrement in ankyrin was evident at earlier ages than that for spectrin. These results suggest that the make-up of the neuronal cytoskeleton changes with age.