Astrocytes are a target for steroid hormones and for steroids produced by the nervous system (neurosteroids). The effect of gonadal hormones and several neurosteroids in the formation of gliotic tissue has been assessed in adult male rats after a penetrating wound of the cerebral cortex and the hippocampal formation. The hormones testosterone, 17beta-estradiol and progesterone and the neurosteroids dehydroepiandrosterone, pregnenolone and pregnenolone sulfate resulted in a significant decrease in the accumulation of astrocytes in the proximity of the wound and in a decreased bromodeoxyuridine incorporation in reactive astrocytes. Of all steroids tested, dehydroepiandrosterone was the most potent inhibitor of gliotic tissue formation. These findings suggest that neurosteroids and sex steroids may affect brain repair by down-regulating gliotic tissue.