The placenta serves in immunological defense of the fetus, providing proteins essential for innate immunity. Maternal and fetal portions of two mammalian placenta types, discoid, and cotyledonary, were separated and analyzed for antibacterial activity using a culture-independent method. Antibacterial activity was detected in both maternal and fetal portions of all placenta types tested. Protease resistance and increased activity after boiling suggests that the factor is activated upon release from a larger molecule. Identification of this factor and the mechanism of activation will lead to a better understanding of the innate immune function provided by the placenta.