A cell surface component has been identified that is found on cultured rat dorsal root ganglion neurons and Schwann cells and also cultured brain astrocytes and oligodendrocytes. This component was detected with a monoclonal antibody originally generated to the NG108 (N18 mouse neuroblastoma X C6 rat astrocytoma) hybrid cell line. The antibody, designated B2C11, binds to cultured peripheral nervous system cells: intact dorsal root ganglion and trigeminal neurons and cultured dorsal root ganglion and sciatic nerve Schwann cells. The binding of B2C11 to dorsal root ganglion neurons in vivo was confirmed by immunofluorescence analysis of cryostat sections. However, cultured embryonic rat central neurons showed no detectable binding of B2C11. Cultured brain cells containing glial fibrillary acidic protein (astrocytes) and also oligodendrocytes cultured from corpus collosum did bind B2C11 on their surfaces. B2C11 immunoprecipitation of detergent-solubilized membrane proteins from both lactoperoxidase iodinated C6 and PC12 rat pheochromocytoma cells indicated a single band with an apparent molecular weight of 21,000-23,000. Analysis of B2C11 binding to particulate protein preparations from adult rat organs showed highest specific activity in dorsal root ganglia. Other neural tissues had substantial binding. Some nonneural tissues (lung, kidney, and small intestine) expressed significant antigen levels, whereas others (heart, liver, and skeletal muscle) had a B2C11 antigen-specific activity less than 5% of that of dorsal root ganglia. Thus the B2C11 antigen is enriched in neural tissues, where it is found on the surfaces of a unique set of neuronal and glial cells.