In cattle, maternal recognition of early pregnancy depends on the effects of the embryonic signal interferon (IFN)-τ. IFN-stimulated genes have been upregulated in the maternal liver during early pregnancy. In this study, primary hepatocyte cell culture models were evaluated for their suitability to test Type I IFN effects invitro. The expression of target genes (interferon-stimulated gene 15 (ISG-15), interferon-induced GTP-binding protein (MX-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-5, insulin-like growth factor 1 (IGF-1), IGF binding protein 2 (IGFBP-2)) was measured using reverse transcription-quantitative polymerase chain reaction in hepatocytes from monoculture or in indirect coculture with Kupffer cells (HKCid) on Days 1, 2, 3 and 4 of culture (n=21 donor cows). Gene expression was also measured on Day 4 after challenging the cultures with recombinant IFNτ, IFNα, progesterone (P4), IFNτ+IFNα or IFNτ+P4 for 6h. A significant increase in the mRNA expression of target genes in hepatocytes was shown in response to stimulation with IFNτ. The Kupffer cells in coculture did not influence the effects of IFNτ in hepatocytes. In conclusion, primary bovine hepatocyte cultures are suitable for stimulation experiments with Type I IFNs and as an extrauterine model for embryo-maternal communication. The proposed endocrine action of IFNτ in the liver may affect maternal metabolism and immune function in the liver.