A twofold increase in the prevalence of depression among women has been consistently observed. Several possible explanations, including methodological, endocrine, psychosocial, and genetic factors, have been proposed for the increased rates of depression among women. This paper describes the analysis of data from a family-genetic study of depressed probands to examine whether genetic factors can explain the preponderance of depressed females. Our data indicate that the excess of females with major depression cannot be attributed to increased genetic loading for depression in women. Other factors which may explain increased rates of major depression in women are discussed.