Microchimerism, the persistence of foreign cells thought to derive from previous pregnancies, has been associated with autoimmune diseases. A maternal parent-of-origin effect in MS remains unexplained. We tested for microchimerism in monozygotic and dizygotic twin-pairs with MS. Microchimerism was associated with MS in affected females from monozygotic concordant pairs when compared to both affected (p=0.020) and unaffected (p=0.025) females in monozygotic discordant pairs. Microchimerism was increased in affected females of dizygotic discordant pairs (p=0.059). The rate of microchimerism was significantly higher in affected twins than in unaffected co-twins (p=0.0059). These observations show an association in twins between the presence of microchimerism and having MS.