Serially sectioned human and squirrel monkey labyrinths were analyzed with high-resolution light microscopy after using 25 different monoclonal antibodies (mAbs) identifying all three main classes of cytoskeletal proteins. A high degree of similarity was found in labyrinths from man and squirrel monkey. Only 1 of 25 mAbs stained differently between the two species. In the squirrel monkey but not in the human the mAbs identifying S-100 proteins stained subpopulations of type I vestibular hair cells in the striola of the two macula and the summit of the cristae as compared to the same type of hair cells in the periphery of vestibular organs. Such an establishment of subpopulations of hair cells with the same ultrastructure has previously not been described in higher vertebrates. In contrast to the species differences in the distribution of neuroactive substances, the cytoskeletal architecture seems to be relatively unchanged and stable during evolution. Since each species has its own hearing and equilibrium function, neurotransmitters (neuropeptides, amino acids, etc.) could contribute to such species-specific functions.