Two large Danish pedigrees with manic-depressive illness (MDI) were ascertained through bipolar probands. The pedigrees include bipolar as well as unipolar cases. An autosomal dominant mode of inheritance with incomplete penetrance was assumed. Linkage relationships between MDI and 37 autosomal serum, enzyme and blood group markers were investigated. For phosphoglycolate phosphatase, a maximum lod score of 2.20 at 0% recombination was found for the largest family. The other family was not informative. This may suggest assignment of a major gene for MDI to chromosome 16p13.