We have identified a Scandinavian family with protein S deficiency using a two-step immunoradiometric method for the determination of the total amount of protein S in plasma. The pattern of the deficiency in the family was compatible with an autosomal, dominant inheritance. Three of 4 members with protein S deficiency had suffered recurrent thromboembolic episodes (leg vein thrombosis, pulmonary embolism, superficial thrombophlebitis). One 38-year-old patient had never shown signs of thromboembolic disease. Analysis of the fibrinolytic system disclosed that this patient had a high activity in blood of the tissue-type plasminogen activator (t-PA), whereas the 3 thrombosis-prone relatives had t-PA activities in the lower part of the reference interval. Our observations suggest that the increased activity of the fibrinolytic system might be of importance for the protection against thrombosis in patients with protein S deficiency. Future studies of larger groups of patients are needed to substantiate the role of the fibrinolytic system in the clinical expression of heterozygous protein S deficiency.