The influence of 38 IgG fractions with either cardiolipin antibodies only (CLa) or both CLa and lupus anticoagulant activity (LA) on the response to activated protein C (APC) and on the snake venom activation of protein C were investigated. Five of eight IgG fractions with LA activity showed a tendency to reduce the effect of APC in the aPTT method and to simulate the APC-resistance phenomenon. This effect was not observed in IgG fractions without LA activity. The addition of IgG fractions did not decrease enzymatic activation of protein C in normal plasma. No correlation was found between sample protein C activity and CLa level or the extent of clotting time prolongation. These observations suggested that acquired resistance to APC in the presence of some types of phospholipid antibodies may be a cause of thrombophilia in such patients.