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The classical method of evaluating whether genetic factors are involved in the etiology of a given disease and to what extent is the twin method. However, methodological problems are great, and it is possible only in a few countries to apply this method to multiple sclerosis (MS) research. To draw genetical conclusions it is of fundamental importance that the material should be an unselected, unbiased material derived from a twin population. Another fundamental point is the diagnosis of twin zygosity. In MS research the twin method has been applied by several authors, but a Mendelian mode of inheritance has not been shown to exist. However, an association of MS to the genetic HLA system has been demonstrated, and this suggests that genetical factors are of some importance in the development of MS. Methodological problems are discussed and the most important twin studies in MS, including the Danish twin study.