Jimpy is a shortened life-span murine mutant whose genetic disorder results in a severe hypomyelination in the central neruons system associated with a variety of glial abnormalities, including oligodendrocyte death. In this study, we report that oligodendrocyte death in jimpy occurs through an apoptotic mechanism, as demonstrated by in situ labeling of nuclear DNA fragmentation. Compared to those of normal littermates, the spinal cords of jimpy mice showed a significantly higher number of apoptotic cells. Our observations also corroborate that specific glial cell death in jimpy is restricted to oligodendrocytes, as evidenced by double labeling for DNA fragmentation and MBP immunocytochemistry. Cells labeled for DNA fragmentation were always negative for astroglial or microglial markers. Apoptotic oligodendrocytes were not aggregated into clusters and were ubiquitously distributed throughout the jimpy spinal cord, although were more numerous in white matter than in gray matter. We found no physical association between astrocytes and dying cells in jimpy. Microglial cells, however, were found closely attached to and even surrounding apoptotic cells. The possible role of microglial cells in relation to apoptotsis is discussed.