Previous studies in this laboratory have led to the identification and purification of a chicken cell surface protein named "neural cell adhesion molecule" (N-CAM) that is involved in neural cell-cell and neurite-neurite interactions. In the present investigation, we have found that a similar molecule exists in the mouse and have confirmed that it is also present in rat neural tissue. A monoclonal antibody to chicken N-CAM that crossreacted with mouse and rat brains and an independently derived monoclonal antibody to mouse N-CAM were used to purify an antigen from perinatal mouse and rat brains. The purified neural antigen resembles chicken N-CAM in its ability to neutralize antibodies that inhibit neural cell aggregation and also in its biochemical properties including molecular weight, sialic acid content, amino acid composition, and autoconversion to a smaller polypeptide. Like chicken N-CAM, the murine molecule is found throughout the nervous system and over the entire neuronal cell surface. These results strongly suggest that the molecule is evolutionarily related to chicken N-CAM and prompt the hypothesis that cell adhesion involving N-CAM is a fundamental mechanism existing in nervous systems of different phylogenetic classes of animals.