In ruminants, the elongating conceptus secretes interferon tau (IFNT), the pregnancy recognition signal, and prostaglandins (PGs). Progesterone from the ovary induces prostaglandin synthase two (PTGS2) and hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) in the endometrial epithelia, and PTGS2-derived PGs regulate endometrial functions and conceptus elongation. The enzyme HSD11B1 interconverts inactive cortisone and active cortisol. These studies determined the effects of pregnancy, IFNT, and PGs on endometrial HSD11B1 expression and activity in the ovine uterus. Study one found that HSD11B1 activity was present in both the endometrium and conceptus during early pregnancy. In study two, ewes received intrauterine infusions of vehicle as a control (CX) or meloxicam (MEL), a PTGS2 inhibitor, from Days 8 to 14 of pregnancy. Endometrial HSD11B1 activity and cortisol in the uterine lumen were substantially lower in MEL-infused ewes. In study three, cyclic ewes received intrauterine infusions of vehicle as a CX, MEL, recombinant ovine IFNT, or IFNT and MEL. Infusion of IFNT increased endometrial HSD11B1 expression and activity and cortisol in the uterine lumen, and this effect was diminished by coinfusion of MEL. In study four, cyclic ewes were infused with vehicle as a CX, IFNT, PGE2, PGF2 alpha, or PGI2. Infusion of all the PGs and IFNT increased endometrial HSD11B1 expression and activity, and IFNT and PGI2 infusion increased cortisol in the uterine lumen. These studies support the idea that IFNT and PGs from the conceptus regulate endometrial HSD11B1 expression and activity that regenerates bioactive cortisol in the ovine uterus during early pregnancy to influence endometrial functions and conceptus elongation.