Although female mice readily reject organs from allogeneic or semiallogeneic male donors, they do not reject the fetuses sired by those same donors. An explanation for this that has been made in the past is that the fetus influences its mother's immune response by sending fetal cells into the maternal circulation. To determine the frequency and magnitude of fetal to maternal cell migration, we employed a sensitive quantitative PCR technique to assess the numbers of male cells in the thymus, spleen, liver, lymph nodes, and peripheral blood of normal mice undergoing their first pregnancy. We found that fetal cell migration is not universal but occurs in only a fraction of pregnancies. Using a kinetic analysis of normal mice mated to syngeneic or allogeneic males, a comparison of normal and SCID mice, and testing of multiparous mice for CTL against fetal Ags, we found that migrating fetal cells were cleared by the maternal immune system. Thus the mother is not continuously exposed to circulating fetal cells and, in fact, has the capacity to eliminate them without eliminating the fetus.