The prolactin (PRL) family of hormones/cytokines is involved in the maintenance of pregnancy and adaptations to physiological stressors. In this report, we identify and characterize a new member of the rat PRL family, examine the impact of maternal hypoxia on placental PRL family gene expression, and investigate maternal adaptive responses to hypoxia. Perusal of the PRL gene family locus in the rat genome resulted in the identification of a putative new member of the rat PRL family. The new member is closely related to the previously reported PRL-like protein-F (PLP-F) and has been named PLP-F and the originally characterized PLP-F, now termed PLP-F. The two proteins exhibit structural similarities but possess distinct cell- and temporal-specific expression profiles. In vivo hypoxia stimulates placental PLP-F and PLP-E mRNA expression in the rat and mouse, respectively. Rcho-1 trophoblast cells can differentiate into trophoblast giant cells, express PLP-F, and exhibit enhanced PLP-F mRNA levels when cultured under low oxygen tension (2%). Exposure to hypobaric hypoxia during latter part of pregnancy did not significantly impact the expression of PLP-F mRNA. Finally, exposure to hypobaric hypoxia during midpregnancy led to increased maternal red blood cells, hemoglobin concentrations, hematocrit, and increased concentrations of maternal splenic mRNAs for key proteins involved in hemoglobin synthesis, erythroid Krüppel-like factor, erythroid 5-aminolevulinate synthase-2, and -major globin. In summary, adaptive responses to maternal hypoxia include activation of placental PLP-F/E gene expression, which may then participate in maternal hematological adjustments required for maintaining maternal and fetal oxygen delivery.