Family study data on unipolar affective illness are analyzed by multiple threshold models of inheritance that incorporate sex effect. In these models males and females share a common genetic-environmental liability, but the less prevalent sex, i.e., males, has a higher genetic threshold for the disorder. Neither single major locus (SML) nor multifactorial-polygenic (MFP) transmission can account for the sex differences in the morbid risk for unipolar disorder. The implications for genetic research in affective disorders are discussed.