Hormone replacement therapy as a means to prevent age-related cognitive decline is controversial due to the type and timing of HRT. We have found that type of estrogen (estradiol v. estrone) can influence cognitive performance and hippocampal neurogenesis. Previous reproductive experience (RE) influences the female brain’s ability to respond to different estrogens later in life. RE influences cognition in middle-age. The present study aimed to illuminate how RE affects different estrogens ability to effect hippocampus structure and function. Multiparous (retired breeders) or nulliparous (never mothered) female rats were ovariectomized (OVX) or sham OVX at 12 months. Rats were administered estrone, 17b-estradiol, 17a- estradiol, or vehicle for 3 weeks and performed Morris water task. Brain tissue was processed for zif268 (immediate early gene) immunohistochemistry. Optical densities of the granule cell layer (GCL) of the dentate gyrus were measured. Results indicate that OVX multiparous rats performed worse on reference memory version of Morris water task compared to OVX nulliparous rats. Interestingly hormone status interacted with RE to influence spatial memory. OVX enhanced spatial memory (probe trial) in multiparous rats but impaired recall in nulliparous rats. In nulliparous rats, estrone and 17b -estradiol treatments enhanced while 17a-estradiol treatment impaired memory recall compared to vehicle treatment. In multiparous rats, estrogens did not influence spatial memory compared to vehicle. Zif268 expression in the dorsal GCL was reduced in multiparous rats treated with estrone compared to OVX vehicle treated multiparous rats. Importantly, spatial memory was positively correlated with zif268 expression in the dorsal GCL in multiparous rats treated with 17a-estradiol (r = 0.69) and 17b-estradiol (r = 0.68), but not estrone. Understanding how different estrogens affect the aging female brain and cognition are beneficial for tailoring HRT treatment to women who have had differing reproductive experiences. Funded by AD Society of Canada to LAMG.