A 66-year-old man with the lupus anticoagulant-hypoprothrombinemia syndrome was treated with cyclophosphamide and prednisone to correct a factor II deficiency prior to elective major surgery. Whereas the lupus anticoagulant activity persisted, functional factor II levels normalized and he underwent surgery without a bleeding diathesis. Immunosuppressive therapy may temporarily normalize factor II levels in patients with the lupus anticoagulant-hypoprothrombinemia syndrome and reduce the risk of excessive hemorrhage. The disparate response of the lupus anticoagulant and hypoprothrombinemia to immunosuppression suggests that the lupus anticoagulant did not directly cause the hypoprothrombinemia.