To test the hypothesis that the onset of maternal behavior is stimulated by estrogen, we examined the effects of medial preoptic area (MPOA) or ventromedial hypothalamus (VMH) implants of the antiestrogen 4-hydroxytamoxifen (OH-TAM) on pre- and postpartum maternal behavior and on postpartum estrus in rats. On day 20 of pregnancy, animals were implanted bilaterally with OH-TAM or cholesterol cannulae into MPOA or VMH. Unilateral cannulae of OH-TAM were also placed into MPOA. Females were tested with newborn pups for the onset of immediate retrieval, prepartum, at noon on day 21, at midnight of the day 21, and 1 day following parturition (which occurred on day 22). On the evening of parturition, implanted animals were tested with stimulus males for the occurrence of postpartum estrus. In order to examine the influence of estrogen on maternal behavior in the absence of parturitional experience, antiestrogen-implanted animals were delivered surgically (cesarean section) and were observed for the display of maternal behavior at various times after surgery. At noon of day 21, only a few animals in any group retrieved pups. However, 12 h later, females that received bilateral OH-TAM implants into MPOA remained nonresponsive, while over 80% animals in other groups retrieved and gathered pups. The antiestrogen did not disrupt the display of postpartum maternal behavior in those females that were allowed to undergo normal parturition, but it significantly reduced the number of cesarean-delivered animals showing maternal behavior. Bilaterial implants of OH-TAM into VMH, but not into MPOA, effectively blocked postpartum estrus. The MPOA implants of OH-TAM resulted in a significant reduction in cytoplasmic estrogen receptor levels and an increase in nuclear estrogen receptor concentrations. The results of these experiments lend support to the current hypothesis that estrogen acts most effectively in the MPOA to stimulate maternal behavior and in the VMH to facilitate sexual receptivity.