Oligodendrocytes are responsible for myelin formation in spinal cord white matter. In the mature spinal cord, the majority of white matter is localized peripherally. During early development, however, the first oligodendrocyte precursors arise in the ventral ventricular zone of the developing cord. Thus, prior to myelination, both migration and proliferation of oligodendrocyte precursors must occur. When and where these events occur is currently unclear. In the chick spinal cord, oligodendrocyte precursors express antigens recognized by the monoclonal antibody O4. Here we show that all chick spinal cord oligodendrocytes are derived from O4+ cells and all O4+ cells appear to give rise to oligodendrocytes. Analysis of the number and distribution of oligodendrocyte precursors in chick spinal cord at different stages of development suggests that relatively few cells migrate from the ventricular source which then proliferate extensively in white matter. This migration is guided by general dispersive cues. Clonal analysis of oligodendrocyte development in cultures derived from different regions of the rodent spinal cord indicated that the cells that initially populate dorsal and peripheral spinal cord retained similar clonal properties to those in ventral spinal cord, suggesting the migrating cells were immature, highly proliferative precursors. Consistent with these results, BrdU incorporation studies indicate that glial proliferation is extensive and persistent in postnatal rat spinal cord white matter. Together, these studies suggest that spinal cord white matter is initially populated by very immature precursors that then undergo extensive local proliferation prior to myelination.