Abstract. Somatic cell nuclei can be dedifferentiated in ooplasm from another species, and interspecies cloned embryos can be implanted into the uteri of surrogates. However, no full pregnancies have been achieved through interspecific mammalian cloning. Rat blastocysts transferred into mouse uteri provide a unique model for studying the causes of interspecific pregnancy failure. In this study, intraspecific pregnancy (mouse-mouse) and interspecific pregnancy (rat-mouse) models were established. On Day 9 of pregnancy, the fetoplacental units were separated from the uterine implantation sites and the expression of messenger (m)RNA was quantitated by realtime PCR. We compared the mRNA expression levels of type-1 T helper (Th1) and type-2 T helper (Th2) cytokines, interferon-gamma (IFN-γ), and interleukin-4 (IL-4) in fetoplacental units between intraspecific and interspecific pregnancy groups. The mRNA expression of IFN-γ in the fetoplacental units of the interspecific pregnancy group was significantly higher than that of the intraspecific pregnancy group (P<0.05). The mRNA expression of IL-4 in the interspecific pregnancy group was significantly lower than that in the intraspecific pregnancy group (P<0.05). We also analyzed the ratio of IFN-γ/IL-4 mRNA, and an increased IFN-γ/IL-4 mRNA ratio was observed in the interspecific pregnancy compared with that in the intraspecific pregnancy group. The IFN-γ and IL-4 mRNA expressions indicate that there is a Th1/Th2 imbalance in the feto-maternal interface of interspecific pregnancies. Bias of Th1 cytokine dominance may be a barrier to reproductive success between species. Key words: Interferon (IFN)-γ, Interleukin (IL)-4, Interspecific pregnancy, Mouse, Rat (J. Reprod. Dev. 53: [219][220][221][222][223][224][225][226][227][228] 2007) o far, somatic cell nuclear transfer (SCNT) has succeeded in generating live animals in many species, including sheep, cattle, mice, goats, pigs, rabbits, cats, rats, mules, horses, dogs, and ferrets [1][2][3][4]. However, it is impractical to clone endangered species by intraspecific SCNT because of insufficient numbers of oocytes and surrogate females. So, interspecific SCNT (iSCNT) has been explored to produce cloned offspring, and usually includes interspecific somatic cell nuclear transfer and interspecific pregnancy. In previous research, the oocytes of bovine, sheep, and rabbits have been used for iSCNT, and interspecific reconstructed embryos have been obtained [5][6][7][8][9][10][11][12][13]. Interspecific r e c o n s t r u c t e d e m b r y o s c a n i m p l a n t i n t o interspecific uteri, but only three speices have been successfully cloned by iSCNT [14][15][16]. Bovine ooplasm was capable of reprogramming the banteng [Bos javanicus, listed as a threatened