The authors have devised a pharmacologic approach to block the proliferation of glial cells (gliosis) which follows various forms of trauma to nervous tissue. A method was devised using the incorporation of 3H-thymidine incorporation into DNA of glial cells as a proliferative index following mechanical trauma. Both biochemical and histologic analysis revealed that treatment of lesioned rats with cell-cycle specific antimitotic agents such as cytosine arabinoside reduced glial proliferation as measured by both DNA synthesis and morphologic quantitation of cell numbers around the lesion. Treatment with cytosine arabinoside resulted in the appearance of numerous unusual cells near the lesion, with indications of aborted mitotic spindles in many of these cells. Other antimitotic drugs such as cyclophosphamide and vincristine were also able to inhibit glial proliferation. Additional experiments suggested that immunosuppression prior to lesioning greatly reduced the proliferative response of glial cells.