The feedback effect of systemically administered dexamethasone on basal plasma corticosterone levels and on adrenocortical responses to ether plus skin incision stress were studied in intact rats and in animals with bilateral dorsal or ventral hippocampectomy or fimbria section. It was found that in rats with ventral hippocampectomy or fimbria section, the degree of the feedback was similar to that in intact rats. However, in animals with dorsal hippocampectomy, the inhibitory effect of dexamethasone on basal and stress-induced adrenocortical responses was significantly reduced. These results taken together with previous observations, that section of the dorsal fornix has a similar effect, suggest that dexamethasone exerts its influence on the brain and that the dorsal hippocampal formation participates in the feedback regulation of pituitary-adrenal function. It cannot be excluded, however, that dexamethasone may exert its influence on the pituitary, and the effect observed may be summation of dexamethasone action on the pituitary plus lack of hippocampal input.