The major assumption underlying all X-linkage studies of bipolar disorder has been that a subgroup of manic-depressive illness follows an X-linked dominant mode of inheritance. An evaluation of the segregation patterns in the pedigrees that have been analysed for X-linkage over the past 20 years does not support this assumption, because the formal genetic criteria for an X-linked dominant mode of inheritance are virtually absent. Not a single pedigree has been ascertained in which the segregation pattern is suggestive of the assumed mode of inheritance. This is mainly because segregation ratios characteristic for X-linked dominant inheritance cannot be observed among the offspring of affected males.