In the cow, the embryo during the first three weeks of pregnancy is free living in the uterine lumen and is dependent on the maternal glandular secretions for its nutritional support. If the environment is appropriate, the embryo will develop sufficiently to prevent luteolysis. The aim of this study was to investigate the regulation of factors involved in embryonic-endometrial interactions during early pregnancy. Uterine horn sections were collected from 17 pregnant (PREG), 9 inseminated but no embryo present and 10 uninseminated cyclic control cows on days 12, 14, 16 and 18 after natural oestrus. The latter two groups were combined to form a single non-pregnant (NP) group. Trophoblast sections were also collected from the day 14, 16 and 18 embryos. The mRNA for interferon tau (IFNτ), oxytocin receptor (OTR), oestrogen receptor a (ER), prostaglandin G/H synthase -2 (PGHS-2), insulin-like growth factor (IGF) -I and IGF binding protein -1 (IGFBP-1) was determined by in situ hybridisation using 45 mer oligonucleotide probes end-labelled with35 S. The optical density (OD) readings were measured from the resulting autoradiographs. The expression of IFNτ mRNA in the trophodectoderm did not vary with embryo age. The expression of OTR mRNA in the luminal epithelium was first detectable on day 14 in 2 out of 5 NP cows and increased thereafter. Conversely, OTR mRNA was undetectable in all PREG cows except for one day 18 cow. In the NP cows, the first significant increase in ER mRNA concentrations in the luminal epithelium was observed on day 16. The pregnancy had no effect on ER mRNA concentrations in the luminal epithelium on days 12 and 14, but was significantly reduced on day 16 and was undetectable by day 18. On day 18, PGHS-2 mRNA was detectable in the luminal epithelium of all cows, but was unaffected by pregnancy status. The expression of IGF-I mRNA in the subepithelial stroma was maintained from days 12 to 18, but was reduced in the day 18 NP cows. IGFBP-1 mRNA concentrations in the luminal epithelium peaked on day 14 in both NP and PREG cows. Thereafter, concentrations declined in the NP group but were maintained in the PREG animals. In conclusion, the suppression of OTR mRNA expression by the embryo does not appear to require the prior suppression of ER mRNA. The continued expression of IGF-I and IGFBP-1 mRNA is likely to play an important role in the establishment of early pregnancy in the cow.