The available evidence suggests that the puerperium is a period of increased risk for acute episodes of illness in bipolar (BP) women and points to genetic factors as influencing vulnerability to postpartum triggering of such episodes. We have previously reported compelling evidence of familiarity of vulnerability to puerperal episodes in female sibs with BP disorder and find similar familial clustering for episodes of narrowly defined postpartum episodes in siblings with major depression. Molecular genetic approaches hold out the promise of uncovering the nature of the puerperal trigger leading to important improvements in the prevention and treatment of postpartum affective episodes. A research strategy focusing on positional and candidate gene approaches may prove fruitful in the search for susceptibility genes for both postpartum triggering in particular and for the affective disorder diathesis in general. We have identified the subset of families in the Wellcome Trust UK-Irish BP sib-pair molecular genetic linkage genome screen that include at least one female who has suffered an episode of puerperal psychosis. Analysis of this more homogeneous subgroup of families resulted in a genome-wide significant linkage signal (LOD = 4.07) on chromosome 16p13 and genome wide suggestive linkage on chromosome 8q24. We are undertaking association studies in women with postpartum psychosis at a number of candidate genes of interest in BP disorder with an emphasis on those for which the expression is influenced by steroid hormones.