The neural cell adhesion molecules L1 and N-CAM share a common carbohydrate epitope that is recognized by the monoclonal antibodies L2 and HNK-1. The L2/HNK-1 epitope is also present on the myelin-associated glycoprotein (MAG) and secreted J1 glycoprotein, both of which have been identified as cell adhesion molecules. Each of the four adhesion molecules is differentially expressed during development on distinct cell types. Expression of the L2/HNK-1 epitope is regulated independently of the protein backbone, is phylogenetically conserved, and plays a role in cell-cell and, particularly, cell-substrate interactions. Another set of glycoproteins shares a common carbohydrate epitope designated L3. This epitope is present on the novel adhesion molecule on glia (AMOG), L1 and MAG, but not on J1 and N-CAM. As in the L2/HNK-1 family, the number of glycoproteins expressing this epitope is not yet known. It is therefore possible that heterogeneities in carbohydrate structures are associated with different sets of adhesion molecules and may have functional implications.