The effects of estradiol valerate and constant light exposure on the histological appearance of the arcuate nucleus were assessed in female rats. Both of these treatments caused significant increases in the numbers of reactive microglial cells and astrocytic granules in the nucleus. Ovariectomy before either treatment prevented the glial reaction, indicating that the experimental manipulations triggered the secretion of an ovarian product which appears to be selectively toxic to the arcuate nucleus. The fact that monthly injections of estradiol valerate in male rats produced the same profile of degeneration in the arcuate nucleus suggests that the neuropathological agent may itself be estradiol. Ovariectomy also significantly reduced arcuate microglial reactivity associated with normal aging, which suggests that cyclic surges of endogenous estradiol may be capable of gradually producing an arcuate lesion. This phenomenon may accout for the hypothalamic reproductive failure associated with normal aging in the rat.