In mammals, the establishment of pregnancy is dependent upon coordinated biochemical signaling and physical interactions between the developing conceptus and uterine endometrium. These essential forms of communication between the conceptus and its maternal environment result in continued production of progesterone from the corpus luteum (CL) and the initiation of implantation/placentation. During the peri-implantation period, conceptuses in ruminant ungulates secrete interferon-tau (IFNT), which acts on uterine endometrium and attenuates endometrial production of the luteolysin, prostaglandin F2α, resulting in the maintenance of CL function. Expression of the ovine IFNT (olFNT) genes is restricted to the mononuclear cells of the trophoblast and the protein is produced for only a relatively short and discrete window of time during early pregnancy. This review deals with identification, characterization and regulation of IFNT gene transcription, and uterine responses associated with pregnancy establishment in ruminants.