Although several studies have shown that Schwann cells (SCs) and olfactory ensheathing cells (OECs) interact differently with central nervous system (CNS) cells in vitro, all classes of adult myelin-forming cells show poor survival and migration after transplantation into normal CNS. X-irradiation of the spinal cord, however, selectively facilitates migration of oligodendrocyte progenitor cells (OPCs), but not SCs, revealing differences in in vivo migratory capabilities that are not apparent in intact tissue. To compare the in vivo migratory properties of OECs and SCs and evaluate the potential of migrating cells to participate in subsequent repair, we first transplanted freshly isolated GFP-expressing adult rat olfactory bulb-derived OECs and SCs into normal and X-irradiated spinal cords. Both OECs and SCs showed limited survival and migration in normal spinal cord at 3 weeks. However, OECs, unlike SCs, migrated extensively in both grey and white matter of the X-irradiated spinal cord, and exhibited a phagocytic phenotype with OX-42 staining on their processes. If a X-irradiated and OEC transplanted spinal cord was then subjected to a focal demyelinating lesion 3 weeks after transplantation, OECs moved into the delayed demyelinated lesion and remyelinated host axons with a peripheral-like pattern of myelin. These results revealed a clear difference between the migratory properties of OECs and SCs in the X-irradiated spinal cord and demonstrated that engrafted OECs can participate in repair of subsequent lesions.