Estrogen stimulates maternal behavior in rats, but does so most potently when its administration is temporally coupled with the termination of pregnancy. In contrast, this effect of estrogen is blocked when subjects are administered a large dose of progesterone concurrent with estrogen. The current study was performed to examine the neural circuitry influenced by these treatments and pup presentation during the hormonally-mediated onset and inhibition of maternal behavior. In experiment I, estrogen induced c-Fos immunoreactivity (Fos-IR) in the medial preoptic area (MPOA) in virgin rats, but was much more effective when administered to pregnancy-terminated rats, suggesting that pregnancy termination increases MPOA’s susceptibility to the physiological effects of estrogen. In experiment II, administering progesterone concurrently with estrogen in pregnancy-terminated rats strongly inhibited estrogen-stimulated Fos-IR in the MPOA, indicating that the physiological effects of estrogen on the MPOA are blocked if high progesterone levels are maintained. In experiment III, pregnancy-terminated subjects were administered estrogen, progesterone, or both hormones and presented with pups for 2 h. Approximately half of the subjects administered estrogen alone showed maternal behavior, but subjects receiving the other treatments were not maternal. In the MPOA, ventral bed nucleus of the stria terminalis (BSTv), and dorsal and intermediate lateral septum (LSd,i), maternal subjects showed the highest levels of Fos-IR, whereas subjects treated with progesterone alone or progesterone in combination with estrogen showed low levels of Fos-IR. These experiments suggest that estrogen could promote maternal behavior by enhancing pup-stimulated activity in the MPOA, BSTv, and LSd,i, regions believed to constitute the neural circuit that promotes maternal behavior, whereas progesterone could inhibit maternal behavior by inhibiting neural activity in some of these regions.