To investigate the actions of glucocorticoids (GCs) on astrocyte functions, interactions of dexamethasone and immediate early genes (IEGs) were studied in cell cultures of rat cerebral cortical astrocytes. Vasoactive intestinal peptide (VIP) induces rapid c- fos mRNA expression and morphological changes (stellation) in cultured astrocytes. Dexamethasone pretreatment decreases this ligand-induced stellation without affecting levels of c- fos mRNA. Moreover VIP does not induce c- jun, jun-B, and NGFI-A mRNA, suggesting that these IEGs may not mediate ligand-induced stellation. The expression of c- fos, c- jun, jun-B, and NGFI-A mRNA are rapidly induced in cultured astrocytes after treatment with phorbol ester, epidermal growth factor, and basic fibroblast growth factor. Dexamethasone pretreatment has no effect on the IEG response induced by any of these agents, suggesting that GCs may not have direct effects on the promoter of these IEGs in cortical astrocytes.