The expression of the proto-oncogene product fos in noradrenergic neurons of the A2 cell group was studied with immunohistochemistry during the estrous cycle of the rat and after ovariectomy and estrogen treatments. During the estrous cycle the percentage of fos-positive norepinephrine containing neurons was highest at proestrus (39%), followed by estrus (36%) while during diestrus only 4% of the A2 neurons contained immunoreactive fos protein in their nuclei. Ovariectomy caused a further decrease in the number of fos-positive A2 neurons (2%) while long-term estradiol administration partially reversed the effects of ovarian steroid removal (19%). However, 3 h after a single subcutanous injection of estradiol into ovariectomised rats, 79% of the noradrenergic neurons in the A2 area showed fos immunoreactivity in their nuclei. The results indicate that fos-expression in the noradrenergic neurons in the A2 region varies depending upon the circulating estradiol levels. Since norepinephrine stimulates gonadotropin releasing hormone (GnRH) secretion from the median eminence during proestrus and the GnRH neurons do not contain estrogen receptors, it is suggested that the A2 region is, at least in part, responsible for conveying the estrogen signal to the GnRH neurons.