As thrombosis of placental vessels may result in recurrent fetal loss, we analysed 39 consecutive women with recurrent fetal loss of unknown cause for activated protein C resistance. Factor V Leiden (FVL) mutation (19 cases) or APC resistance without FVL (nine cases) were found among these 39 women. Evaluation of 128 pregnancies in 19 patients with factor V Leiden mutation and 56 gestations in nine women with acquired APC resistance, revealed over 50% first-trimester abortions and 17% late abortions. Intra-uterine fetal death occurred in nine out of 19 FVL patients (47%). Only 34 of 184 gestations (18%) in hereditary or acquired APC-resistance women resulted in a live birth, with 11 of the 34 (32%) being premature deliveries. These data suggest that, in some patients with recurrent fetal loss, hereditary and acquired APC resistance are potential causes of vascular placental insufficiency.