A new marker for young oligodendrocytes has been identified by a monoclonal antibody (mOg-1, IgM isotype) prepared from cerebellar plasma membrane stimulated mouse lymphocytes. mOg-1 reactive cells in the mouse cerebellum first appear at day 19 of gestation. Future white matter layers of fixed sections of neonatal rat cerebellum were labeled with mOg-1. Although EM analysis has shown cell-surface binding by presumptive oligodendroglia in neonatal cerebellum, the antibody does not bind to compact myelin. In cell cultures prepared from L-d-old mice, 1.1% of the cells bound mOg-1 after 3 d in culture, but up to 5% of the cells bound mOg-1 after 2 weeks in culture. Of these same Og-l-positive cells, 69% bound anti-gabtctocerebroside and 65% bound anti-myelin basic protein. After a week in culture Og-l-positive cells often produced lamellar sheets extending a millimeter over the polylysine substratum in the absence of normal myelin formation. mOg-1 recognizes a cell-surface determinant distinct from well-characterized oligodendroglial molecules (galactocerebroside, sulfatide and myelin basic protein) that is expressed early in oligodendrocyte development. The antibody has been used to follow the maturation of oligodendrocytes in cultures of both normal and jimpy mouse cerebellum.The nervous system is a complex network derived from multiple associations between different cell types. The limited number of distinct cell types and the availability of neurological mutants with defective cerebellar histogenesis make the mouse cerebellum an attractive model for studying cell-cell interactions.The development of antibodies toward neural cell-surface molecules could be instrumental in establishing the role of specific determinants in histogenesis. We have used the hybridoma technology of Milstein (1975, 1976) In this report, we describe a monoclonal antibody (mOg-1) reactive with the surface of young oligodendrocytes, prior to the Received Dec. 19, 1985; revised Mar. 4, 1986; accepted Mar. 4, 1986. We woula like to thank Dr. Robert Lasher for his helpful discussions and S.Hat&e for her expert assistance. We thank Drs. Dahl, De.Vellis, Evans, Habig, Qua&s, Ranscht, and Rapport for their generous girt of antisera and tetanus toxin used in these studies. Some of these studies were submitted in partial fulfillment of the requirementi for the Doctor of Philosophy degree from the University of Colorado (1983). This work was su~ucwted in nart bv USPHS Grants NS-098 18and T32-bM-07342.