To determine if cell recognition molecules interact trophically with oligodendrocytes (OCs), their effect as growth substrates for differentiating oligodendroblasts was studied in primary culture. Oligodendroblasts purified from postnatal rat cerebrum by immunopanning were plated on substratum-bound cell adhesion molecules or extracellular matrix glycoproteins in chemically defined medium in which OCs terminally differentiate but survive poorly. Growth on myelin-associated glycoprotein (MAG) and neural cell adhesion molecule (N-CAM) selectively increased the number of viable cells per culture 2 weeks after plating as much as tenfold and sixfold, respectively, over background survival on an albumin substrate, whereas L1, tenascin-R, tenascin-C, fibronectin, and laminin were ineffective. Neither MAG nor N-CAM stimulated bromodeoxyuridine incorporation into cultures, indicating that enhanced proliferation did not contribute to better survival. Compared to growth on polyornithine alone, oligodendroblast differentiation in the added presence of MAG or N-CAM was qualitatively unchanged; > 90% of surviving cells developed into OCs that matured further by immunocytochemical and morphological criteria. A striking difference, however, was the quantitative effect of MAG and N-CAM substrates on oligodendrite outgrowth, increasing myelin-like membrane formation two- to threefold (> 8 x 10(3) microns2/cell). These findings support the concept that autotypic or heterotypic cell contact-mediated signaling by recognition molecules at the OC surface contributes trophic support of myelinogenesis.