Microchimerism (MC) is the stable presence of small numbers of non-host cells and appears to be commonly present in parous women. There are several methods of detecting microchimerism and each has advantages for different types of studies, but the risk of contamination and the differing levels of sensitivity lead to difficulties in estimating the proportion of individuals that are microchimeric. Recent observations of an increased frequency of microchimerism in women with scleroderma and Hashimoto's thyroiditis suggest that microchimerism may increase the risk of developing autoimmune disease. Inferences regarding autoimmunity are drawn from the immunological effects of organ and bone-marrow transplantation. Potential research questions regarding microchimerism, human leukocyte antigen (HLA) similarity, and autoimmune diseases in the context of multiple sclerosis (MS) are discussed.