The influence of glucocorticoids on the transcription factor NFkB was investigated by using the gel mobility shift assay with nuclear extracts prepared from rat cerebral cortex and hippocampus after a variety of in vivo treatments. Following stimulation with each of three treatments, kainate, pilocarpine, or lithium plus pilocarpine-induced seizures, NFkB DNA binding activity was significantly greater in the cortex and hippocampus from adrenalectomized than from adrenal-intact rats. These results indicate that in rat brain glucocorticoids inhibit NFkB activity in addition to the previously reported inhibition of the transcription factor AP-1 (activator protein 1). Impairment of stimulus-induced transcription factor activity may contribute to the deleterious effects of prolonged elevations of glucocorticoids on neuronal function. © 1995.