After a description of threshold models of familial transmission based on an underlying continuous liability distribution, family data from the NIMH-CRB Collaborative Psychobiology of Depression Program-Clinical are described. No sex differences are found for bipolar illness, whereas female relatives have an increased rate of primary unipolar illness when compared to male relatives. This effect persists when relatives are classified according to recurrence, current illness, onset within the last 10 years, and treatment. Moreover, a cohort effect is present in the data and indicates a sex ratio close to one in the young cohort (less than or equal to 25). We considered the transmission of illness from parent to offspring by using survival analysis to examine the proportion of ill brothers and sisters of probands according to the affection status of parents. A maternal effect is found, with the mother having a greater influence on the liability of offspring of either sex. This is at odds with the notion that males and females have identical liabilities, but females have a lower threshold reflecting acknowledgement of more symptoms, etc. However, the mean difference in liability between the sexes may be due to systematic biological/cultural differences, with parental transmission contributing to variation about their means.