The vital role played by prolactin during pregnancy and lactation is emphasized by the physiological adaptations that occur in the mother to maintain a prolonged state of hyperprolactinemia. In many species the placenta provides a source of lactogenic hormones in the circulation, ensuring the continued presence of a hormone capable of activating the prolactin receptor throughout pregnancy. In addition, the tuberoinfundibular dopamine neurons, which normally maintain a tonic inhibitory influence over prolactin secretion, show a reduced ability to respond to prolactin during late pregnancy and lactation, allowing high levels of prolactin to be maintained unopposed by a regulatory feedback mechanisms. There is clear evidence that systemic prolactin gains access to the cerebrospinal fluid, from where it can diffuse to numerous brain regions. Prolactin receptors are expressed in several hypothalamic nuclei, including the medial preoptic and arcuate nuclei, and we have observed marked increases in expression of prolactin receptors in these nuclei during lactation. Moreover, a number of hypothalamic nuclei, including the paraventricular, supraoptic and ventromedial nuclei, in which prolactin receptors were not detected in diestrous rats, were found to express significant amounts of prolactin receptor during lactation. These observations have important implications for the variety of documented actions of prolactin on the brain. Prolactin has been reported to influence numerous brain functions, including maternal behavior, feeding and appetite, oxytocin secretion, and ACTH secretion in response to stress. In light of the high circulating levels of prolactin during pregnancy and lactation and the increased expression of prolactin receptors in the hypothalamus, many of these effects of prolactin may be enhanced or exaggerated during lactation. Hence, prolactin may be a key player in the coordination of neuroendocrine and behavioral adaptations of the maternal brain.