The low density lipoprotein receptor-related protein (LRP) Is a large multifunctional clearance receptorthat has been implicated In the hepatlc uptake of chylomicron remnants and In the removal of protease-inhibitor complexes from the circulation and from the extracellular space. Disruption of the LRP gene in mice blocks development of LRP-‘-embryos around the implantation stage. The expression pattern of LRP in the postlmplantation stage embryo is identical to that of urokinase, a plasmlnogen activator that confers invasive properties to migrating cells. We demonstrate that LRP mediates uptake and degradation of urokinase-type plasminogen activator-plasminogen activator inhibitor 1 complexes and propose that the Inability of the giant cells to remove the inactive protease complexes from their surfaces interferes with implantation of the embryo.