Proliferation of glial cells is one of the hallmarks of CNS responses to neural injury. These responses are likely to play important roles in neuronal survival and functional recovery after central or peripheral injury. The boundary between the peripheral nervous system (PNS) and CNS in the dorsal roots, the dorsal root transitional zone (DRTZ), marks a distinct barrier for growth by injured dorsal root axons. Regeneration occurs successfully in the PNS environment, but ceases at the PNS-CNS junction. In order to understand the role of different glial cells in this process, we analysed the proliferation pattern of glial cells in central (CNS) and peripheral (PNS) parts of the dorsal root and the segmental white and grey spinal cord matter after dorsal rhizotomy or sciatic nerve transection in adult rats 1-7 days after injury. Monoclonal antibody MIB-5 or antibodies to bromodeoxyuridine were used to identify proliferating cells. Polyclonal antibodies to laminin were used to distinguish the PNS and CNS compartments of the dorsal root. Dorsal root lesion induced glial cell proliferation in the CNS as well as PNS beginning at 1 day, with peaks from 2 to 4 days postoperatively. After sciatic nerve injury, cell proliferation occurred only in the CNS, was minimal at 1 day, and peaked from 2 to 4 days postoperatively. Double immunostaining with specific glial cell markers showed that after dorsal root transection 60% of the proliferating cells throughout the postoperative period examined were microglia, 30% astrocytes and 10% unidentified in the CNS, while in the PNS 40% were Schwann cells, 40% macrophages and 20% unidentified. After sciatic nerve injury virtually all proliferating cells were microglia. These findings indicate that non-neuronal cells in the CNS and PNS are extremely sensitive to the initial changes which occur in the degenerating dorsal root axons, and that extensive axonal degeneration is a prerequisite for astroglial and Schwann cell, but not microglial cell, proliferation.