Significance Prolactin-responsive neurons in the medial preoptic area project widely throughout the brain. After targeted deletion of prolactin receptors in the preoptic area of adult female mice, mice were able to get pregnant and give birth normally. However, mothers lacking prolactin receptors in the medial preoptic area abandoned their litters soon after birth, establishing a critical role for prolactin/placental lactogen action in this area for establishment and maintenance of normal parental care.