Apoptosis within villous trophoblast is increased in pregnancies complicated by pre-eclampsia (PE). Caspase activity is regulated by the balance of inhibitors of apoptosis proteins (IAPs). This study investigated the expression and localisation of smac, HtrA2/Omi and IAPs in villous trophoblast in normal pregnancies and those complicated by PE. smac was significantly elevated in PE compared to normal pregnancies and staining was evident in syncytiotrophoblast (ST), cytotrophoblast (CT) and endothelial cells. Weak staining for HtrA2/Omi was present in ST cytoplasm in both normal and PE pregnancies. XIAP and survivin were not altered in PE. XIAP localized to ST cytoplasm, with weak staining in CT. Survivin localized to ST and CT cytoplasm, but also CT nuclei. In non-placental cells increased smac expression in the presence of normal IAP expression induces apoptosis. In conclusion, the increased expression of smac in villous trophoblast may have a role in increased apoptosis in PE.