The widespread distribution of mRNA encoding orexin- 1 (OX1R) and -2 receptors (OX2R) in the central nervous system suggests that orexin may be involved in multiple functional pathways. Central administration of orexin stimulates feeding and also affects ovarian steroid-dependent luteinizing hormone secretion, suggesting involvement of orexin in the regulation of reproductive function. To investigate a possible role for orexin in reproductive function, we examined variations in prepro-OX, OX1R, and OX2R mRNA levels in the female rat hypothalamus during the estrous cycle, pregnancy, parturition, and lactation using competitive reverse transcription-polymerase chain reaction. During the estrous cycle, only OX1R mRNA expression during late proestrus was significantly higher than that at metestrus. The prepro-OX and OX1R mRNA levels on d 1 of lactation were significantly higher than that during late pregnancy and lactation. Immunohistochemistry revealed the presence of orexin-A immunoreactive cells and the OX1R subtype in the lateral hypothalamic area as well as the magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei, respectively, in pregnant and lactating rats. These results suggest a role for orexin in reproduction that may be involved in regulating physiological function in early lactation through important binding sites in hypothalamic PVN and SON.