The molecular and cellular basis of the psychotropic actions of adrenal corticosteroids is poorly understood. Previously, we reported that modulation of large conductance Ca2+-activated potassium channel (BK-channel) function by glucocorticoids can be recapitulated in human embryonic kidney293 (HEK293) cells (J Physiol 537:57, 2001). In the present paper, we examined the effect of dexamethasone on the expression of candidate mediator proteins of glucocorticoid action, dex-ras1 and serum and glucocorticoid inducible protein kinase 1 (SGK), in HEK293 cells. Dex-ras1 mRNA was readily detectable under basal conditions however, no changes of dex-ras1 mRNA expression occurred upon exposure to 100 nM of dexamethasone for 2 h. In contrast, a 2.5-fold increase of SGK mRNA was found under similar conditions. Total levels of cellular SGK protein were unaltered upon exposure to dexamethasone, but a marked increase of SGK in a Triton-X100 insoluble fraction was observed. BK-channel alpha-subunits could not be co-immunoprecipitated with SGK. In summary, SGK, but not dex-ras1, mRNA is rapidly induced by glucocorticoid stimulation in HEK293 cells. However, there appears to be no direct protein-protein interaction between SGK and BK-channel alpha-subunits.