Binucleate giant cells (BNC) decline in number and viability peripartum if the placenta is subsequently released normally. This suggests an involvement of BNC destruction in fetal membrane separation in the cow. Dexamethasone induction of parturition may result in fetal membrane retention through a stabilization of the BNC (possibly the BNC plasma membranes). Prostaglandin F2a treatment in vitro induced a loss of BNC when these were obtained from cows which subsequently retained the fetal membranes for a longer than normal interval. Overall, our results indicate an involvement of BNC loss and breakdown in placental separation and a possible involvement of prostaglandins and glucocorticoids in modulating this process.