We report on a newly diagnosed family with hereditary antithrombin III deficiency, with thromboembolic complications in the propositus. Both the propositus and his asymptomatic sister had decreased plasma levels of antithrombin III antigen and activity (28-52% of normal with good agreement between functional and immunologic assays). The propositus developed deep venous thrombosis, followed by massive pulmonary emboli despite heparin therapy and was treated with streptokinase and heparin with excellent results. Shortly thereafter, small bowel obstruction required surgical intervention, and antithrombin III concentrate, recently available in the United States as an investigational new drug (I.N.D.), was administered with no postoperative thrombotic complications. He was subsequently asymptomatic while on warfarin prophylaxis but twice developed venous thrombosis when he failed to take warfarin. The addition of danazol therapy led to a sustained rise in the antithrombin III level. Each of these therapeutic approaches is discussed and the literature reviewed with emphasis on the newer agents--streptokinase, antithrombin III concentrate, and danazol.