The implication of cell adhesion molecules (CAMs) in the mediation of the immune response to inflammatory stimuli has been shown in different neurological syndromes. The neural cell adhesion molecule (NCAM) and the myelin associated glycoprotein (MAG) are functionally important CNS-cell adhesion molecules (CAMs) and members of the immunoglobulin gene superfamily (IgSF). Both CAMs are expressed from the time of neuronal induction and myelin formation and are likely to contribute to the generally adhesive properties of neurons and oligodendrocytes. The present study describes, by means of SDS-PAGE and immunoblotting, a novel CNS antigen which is a glycoprotein detected in post mortem frontal lobe tissue of ten subjects at an M(r) 65 and 113 kD which showed the greatest sequence homology to neuronal IgSF members like NCAM. This expected membrane CAM, with probable functions in CNS cell-cell interactions, had been detected first in primary human melanoma cells, with increasing expression as tumors progress and is expected to be a developmentally regulated CAM in neuroectodermal tissues.