Neurons and glia interact in the development of mammalian central nervous systems and in the maintenance of stable myelinated axons. Recent evidence suggests a role for oligodendrocytes in providing trophic support for neurons during development and in the mature nervous system. This work prompted us to study oligodendrocyte influences on neuronal survival and death in vitro. Rat embryonic cortical neurons were co-cultured with purified oligodendrocytes at different developmental stages and separately with oligodendrocyte-conditioned medium. Neuronal survival was measured by immunocytochemistry and 3H-GABA uptake. Neurons show a marked increase in survival when co-cultured directly with oligodendrocyte precursors (OPCs) and differentiated oligodendrocytes. Neurons cultured in the presence of OPCs separated by a permeable membrane and those cultured in medium conditioned by oligodendrocytes also show a significant increase in survival. Medium conditioned by differentiated oligodendrocytes provides a greater survival effect than medium conditioned by OPCs. Neutralising antibodies to IGF-1, but not to other candidate trophic factors, block the soluble survival effect of oligodendrocytes. Cells of the oligodendrocyte lineage produce IGF-1 and recombinant IGF-1 promotes neuronal survival under identical conditions. This study provides evidence that OPCs and differentiated oligodendrocytes support neuronal survival by both contact-mediated and soluble mechanisms and that IGF-1 significantly contributes to this effect. GLIA 36:48–57, 2001. © 2001 Wiley-Liss, Inc.