The effects of cortisol on protein synthesis in distinct brain regions were studied. Hormone administration produced increases in tubulin and actin content in the soluble fraction isolated from septum and hippocampus. Therefore, the poly(A)RNAs were isolated from the same brain regions and their translational capacity was tested in a heterologous cell-free system. Poly(A)RNAs from cortisol-treated animals, as compared to control animals, had a stimulatory effect on 35S-methionine incorporation into tubulin and actin. Thus, our results suggest that cortisol treatment increases the amount of mRNAs coding for tubulin and actin. More importantly, this study indicates that the molecular mechanism of glucocorticoid action in the brain involves modulation of protein synthesis.