The neuron-glia cell adhesion molecule (Ng-CAM) mediates neuron-neuron adhesion by a homophilic mechanism and neuron-astrocyte adhesion by a heterophilic mechanism. The protein is expressed on neurons and Schwann cells but not on astrocytes. It is most prevalent during development on cell bodies of migrating neurons and on axons during formation of nerves. Ng-CAM expression is greatly increased following nerve injury. Anti-Ng-CAM antibodies inhibited migration of granule cells along Bergmann glia in cerebellar explants and fasciculation of neurites in outgrowths from explants of dorsal root ganglia. The combined results indicate that Ng-CAM on neurons binds to Ng-CAM on adjacent neurons and to as yet unidentified ligands on astrocytes. Ng-CAM is synthesized in chicken neurons from a 6 kb mRNA as Mr approximately 200,000 forms which are cleaved to yield two components of Mr 135,000 and 80,000. It is glycosylated and can be phosphorylated. Amino acid sequence analysis indicates that it contains six immunoglobulin domains, five fibronectin type III repeats, a transmembrane domain and a cytoplasmic region. Structural analyses indicate that Ng-CAM is most closely related to the mammalian glycoprotein L1 but significant differences between them strongly suggest that they are not equivalent molecules. The recent identification of another structurally related molecule in the chicken called Nr-CAM underscores the notion that these molecules are members of a subfamily of neural cell adhesion molecules within the immunoglobulin superfamily that have related or complementary functions in the nervous system.