It is now recognized that cells traffic between fetus and mother during pregnancy. Fetal cells have been found to persist for years, probably for a lifetime, in the circulation of normal women. The term chimerism is used when one individual harbors cells from another individual, and the term microchimerism refers to low levels of chimerism. Chronic graft-versus-host disease (GVHD) is a condition of human chimerism that has similarities to some autoimmune diseases. Women have a predilection to autoimmune disease, and human leukocyte antigen (HLA) class II genes are known to be important both in autoimmune disease and in GVHD. Considered together, these observations led to the hypothesis that microchimerism and HLA genes of host and nonhost cells are involved in autoimmune disease. Alternative sources of microchimerism could affect men and women who have never been pregnant, including from a twin, from a blood transfusion, or long-term persistence of maternal cells that have trafficked to the fetal circulation during pregnancy. Studies of systemic sclerosis (SSc), primary biliary cirrhosis (PBC), Sjögren syndrome, pruritic eruption of pregnancy, myositis, and thyroid disease have both lent support and raised doubts about the role of microchimerism in autoimmune disease.