Antithrombin III (AT III) deficiency is associated with a high risk of venous thromboembolism, particularly in pregnancy. As prophylactic treatment it has been recommended that plasma levels of AT III be normalized by use of AT III concentrates, in addition to heparin. - We report on the prophylactic treatment of three sisters (age 21, 25, and 32 years) with congenital AT III deficiency (38-53%, normal 80-120%) and reduced inducible fibrinolytic activity (1.2, 5.8, 1.2%, normal greater than 8.5%), who had already had severe thromboembolism. During pregnancy prophylactic measures were taken individually, depending on the plasma level of beta thromboglobulin (BTG) determined every 2-3 weeks. In two patients prophylaxis with s.c. heparin (2 X 7500 IU/d) was started at the time of the first increase of BTG (around 10th week of gestation), leading to normalization of BTG. When BTG was again elevated, the dose of heparin was increased stepwise to 2 x 15,000 IU/d; in this way functional AT III levels remained in the range of 28-50%. Thus, these two patients received only heparin throughout pregnancy. However, in the third patient BTG levels could not be normalized by heparin alone (60-130 ng/ml, normal less than 43 ng/ml). Injections of AT III concentrate (1000 IU) led to reduction of BTG within 2 hours (60----42,220----61 ng/ml). Therefore, AT III was given from the 25th week of gestation in increasing amounts up to 5000 IU/week (funct. AT III in plasma 51-72%) in addition to heparin (2 x 12,500 IU/d), resulting in BTG levels of 33-51 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)