This study examined the glial cell kinetics and death in the thoracic spinal cord of normal and myelin-deficient (md) rats between 1 and 21 days of age and determined whether the observed glial cell death primarily affected oligodendrocytes and had the morphologic and molecular features of apoptosis. In the md rat spinal cord there was an increase in cell division and death in a pattern that correlated with the onset of myelination. The dying cells were identified as oligodendrocytes ultrastructurally as many had the characteristic distention of the rough endoplasmic reticulum seen in the md rat glia. Double labeling using PLP in situ hybridization and a modified TUNEL method also suggested that the dying cells, in both mutant rats and control littermates, were oligodendrocytes. These findings were compared with previous studies on the md rat optic nerve and those in other PLP mutants.