Mouse trophoblast cells synthesized and secreted proteins during the peri-implantation period, some in the molecular size range of alpha interferons (IFN-α), known mediators of the maternal recognition of pregnancy in sheep and cows. However, conditioned media samples containing secreted proteins from Day-5 mouse blastocysts or from trophoblast outgrowths did not contain detectable levels of antiviral activity indicative of IFN. In addition, it was not possible to induce a decidual reaction in suitably sensitized uteri with intraluminal instillation of IFN-α. The results indicate that IFNs are probably not involved in the maternal recognition of pregnancy at the time of implantation in the mouse.