This chapter describes experimental evidences, which shows that production of early pregnancy factor (EPF) is initiated by fertilization and that its presence in serum monitors the viability of the conceptus for at least the first half of gestation. Furthermore, EPF is necessary for the continued survival of the conceptus. The tissues involved in the production of EPF are discussed and the role of EPF in the maintenance of the embryo is also considered. The role of EPF in maintaining embryonic viability may involve immunological protection. The characteristics of EPF meet the criteria needed for an effective immunosuppressant capable of inhibiting maternal rejection of the embryo. Immunomodulation begins within hours of fertilization and is reversible within 24 hours of loss of the embryo. The effect of EPF is selective; it binds to a specific lymphocyte population, recruiting suppressor cells that in turn release soluble suppressor factors, genetically restricted in their behavior. The target cells affected by these suppressor factors are of the same T-lymphocyte population as those involved in graft rejection. The discovery of EPF and the ensuing research has depended on the activity of EPF in the rosette inhibition test.