The retroplacental compartment in which maternal blood is in direct and continuous contact with trophoblasts derived from the fetus seems to be the place where maternal and fetal cells regulate each others' activities. To assess the role of the retroplacental compartment in the immune regulation of pregnancy, 10 healthy pregnant women were selected for evaluation of the immune activity of their lymphocytes and plasma from the retroplacental blood. The results showed that the proliferation and cytotoxic capacity of these lymphocytes, but not of maternal peripheral lymphocytes, against fetal cells were significantly inhibited in undirect mixed lymphocyte culture and direct cell-mediated cytotoxic assay, respectively. The plasma from retroplacental blood showed significant immunosuppressive properties and depressed the proliferation of maternal peripheral lymphocytes stimulated by fetal HLA as well as the cytotoxic activity of these cells against the fetal lymphocytes. The present data suggest that the retroplacental compartment seems to be an immunosuppressive barrier, protecting the fetus from maternal rejection.