The role of glucocorticoids in the in vivo regulation of glial fibrillary acidic protein (GFAP) was examined. Corticosterone administration to adult rats resulted in decreased levels of GFAP throughout the brain whereas adrenalectomy caused levels of GFAP to increase. Corticosterone administration to adrenalectomized rats lowered GFAP levels to values below those of sham controls. Thus, the expression of GFAP throughout the brain appears to be physiologically regulated by adrenal glucocorticoids.