3 individuals from 2 unrelated families with recurrent thromboses and quantitative deficiencies of antithrombin III (AT-III) were treated with danazol, 600 mg daily for 4 months. Significant increases of AT-III (p < 0.025) measured as heparin cofactor activity were noted in 1 female and 1 male patient. Failure to augment levels in the other male patient may have been due to poor absorption of the drug following small bowel resection for mesenteric infarction. Side effects of estrogen deficiency necessitated dosage reduction in the female patient. The 2 males experienced no adverse side effects except for prolongation of the prothrombin time in 1 who was receiving oral anticoagulants. We conclude that danazol causes a significant increase in some individuals with familial AT-III deficiency. Additional studies are necessary to determine whether this form of therapy may prove to be a suitable alternative to long-term anticoagulation and to assess the long-term clinical benefits in individuals with recurrent thrombosis.