A developmental model of spinal cord injury in the embryonic chick was specifically developed to characterize the involvement of caspases in injury-induced oligodendrocyte apoptosis remote from the lesion and the ability of caspase inhibitors to attenuate this process. Developmental apoptosis in the cervical spinal cord increased within the white matter between embryonic days 13 and 18, the period of myelination of this region. Spinal cord transection during this period induced a rapid increase in apoptotic cells in the ventral and lateral white matter over several millimeters caudal to the injury. Immunostaining identified large numbers of these cells as oligodendrocytes. Catalytic activity assays and immunostaining demonstrated caspase-3-like but not caspase-1-like activity to be involved in this apoptotic response. In vivo application of specific caspase inhibitors significantly attenuated transection-induced apoptosis. Thus, we describe a developmental period during which spinal oligodendrocytes exhibited a heightened, caspase-dependent sensitivity to transection-induced apoptosis that is attenuated by caspase inhibition.