Young adult male rats received subcutaneous implants of Alzet osmotic minipumps which delivered 400 micrograms hydrocortisone per day. Untreated rats received no pumps or pumps containing the vehicle. Five days after receiving the implantation, both groups of rats were subjected to unilateral entorhinal lesion. Seven days after surgery, brains were analyzed quantitatively for glial changes in the denervated dentate outer molecular layer. Numerical densities of astrocytes and nonastrocytic glia were calculated by cell counting using 1.0-micron toluidine blue-stained sections. Glial acid phosphatase staining was quantitated using computer-assisted cytophotometric measurement of individual glial cells. Hydrocortisone-treated animals demonstrated 31% more astrocytes and 22.4% less nonastrocytes in the dentate outer molecular layer compared with untreated animals. Glia in the treated animals also showed a 33% decrease in average optical density of cytoplasmic acid phosphatase staining. These findings suggest that hydrocortisone treatment prior to and following an entorhinal lesion accelerates lesion-induced migration of astrocytes to the outer molecular layer, and reduces the increase in microglial number resulting from the lesion. The observed effect on microglia may result from a direct hormonal inhibition of local proliferation of microglia or from the well known systemic anti-inflammatory action of glucocorticoids on monocytes, the putative precursors of brain microglia. Our findings suggest that glucocorticoid hormones significantly alter the response of non-neuronal cells to neural tissue damage.