Objective: Vulnerability to the triggering of bipolar episodes by childbirth aggregates in families and may define a genetically relevant subtype of bipolar disorder. The authors conducted a search by systematic whole genome linkage scan for loci influencing vulnerability to bipolar affective puerperal psychosis. Method: The authors selected families with bipolar disorder from their previous bipolar disorder genome scan, in which there was at least one family member with a manic or psychotic episode with an onset within 6 weeks of delivery. Individuals were coded as affected if they had been diagnosed with bipolar I disorder; bipolar 11 disorder; or schizoaffective disorder, bipolar type, according to DSM-IV. A total of 36 pedigrees contributed 54 affected sibling pairs to the cohort. A genome scan with 494 microsatellite markers was analyzed using GENEHUNTER and MAPMAKER/SIBS. Results: A genome-wide significant linkage signal was observed on chromosome 16p13, and a genome-wide suggestive linkage was observed on chromosome 8q24. No significant or suggestive linkage was observed in these regions in our original bipolar scan. Conclusions: This study identifies chromosomal regions that are likely to harbor genes that predispose individuals to bipolar affective puerperal psychosis. The identification of susceptibility genes would enhance understanding of pathogenesis and offer the possibility of improvements in treatment and risk prediction.