The ovine conceptus releases interferon-tau (IFNT), which prevents upregulation of the endometrial estrogen receptor (ESR1) and, consequently, oxytocin receptor (OXTR), thereby disrupting pulsatile release of prostaglandin F2alpha (PGF) in response to oxytocin. IFNT, through paracrine action on the endometrium, protects the corpus luteum (CL) during maternal recognition of pregnancy. Pregnancy also induces IFN stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs), which is interpreted to reflect a "prompted" antiviral and immune cell response peripherally in ruminants. IFNT was recently demonstrated to be released from the uterus in amounts of 200 microg (2 x 10(7) U)/24 h via the uterine vein and to induce ISGs in the CL during maternal recognition of pregnancy. Delivery of recombinant ovine (ro) IFNT into the uterine vein in a location that is upstream of the utero-ovarian plexus from Day 10 to 17 maintained serum progesterone concentrations and extended normal 16-17 d estrous cycles to beyond 32 d. It is concluded from these studies that IFNT is released into the uterine vein and initiates a peripheral antiviral response to protect pregnancy from maternal viral infection. It also may have endocrine action through inducing luteal resistance to PGF and longer-term survival of the CL and maintenance of pregnancy.