While glucocorticoids have been shown to exacerbate calcium-induced neuronal damage, little is known about the effects of these hormones on calcium-induced damage to glial cells. Here we examine the effect of synthetic glucocorticoid dexamethasone on calcium ionophore A23187 and serum deprivation-induced damage to rat C6 glioma cells. Treatment of the glioma cells with A23187 reduced cell viability, similar in extent to that observed with serum deprivation. Both A23187 and serum deprivation caused cell damage without degradation of the genomic DNA into nucleosomic fragments. In addition, the reduction in cell viability caused by A23187 was not significantly altered by DEX at concentrations enhancing serum deprivation-induced cell death. These results suggest that the cytotoxic effect of A23187 on glial cells may be mediated through a mechanism different from that underlying serum deprivation-induced cell death, and that, in contrast to calcium-induced neuronal damage, calcium-induced damage to glial cells is likely to be insensitive to glucocorticoids.