Recent studies indicate cells traffic between the fetus and mother during normal human pregnancy and that fetal cells persist in maternal peripheral blood for decades after childbirth. The long-term persistence of fetal cells, when considered together with clinical similarities of chronic graft-vs-host disease and autoimmune disease and the female predilection to autoimmunity, led to the hypothesis that microchimerism is involved in some autoimmune diseases. Sources of engraftment applicable to men and to women who have never been pregnant include from a blood transfusion, a twin sibling, or mother. Initial studies lend support to the hypothesis. A role in disease pathogenesis has not been demonstrated, however, and microchimerism is also common in healthy normals. If microchimerism is involved in the pathogenesis of some autoimmune diseases further understanding potentially may lead to new therapeutic strategies.