The pathogenic mechanisms of thrombosis during inflammatory syndromes are unknown. The aim of our study was to evaluate coagulation activation and fibrinolysis and to study an acquired protein S deficiency in 58 patients with an inflammatory syndrome of neoplastic (16), infectious (24) or systemic (18) origin and in 54 control subjects. The results indicated that coagulation activation, demonstrated by an increase in the prothrombin fragment 1+2, was present in patients with an inflammatory syndrome regardless of its origin. Free protein S, the only functionally active protein, was not reduced even though C4b-binding protein was increased in inflammatory syndromes. Thus, a prothrombotic state was found in inflammatory syndromes but is not explained by an acquired protein S deficiency. All except five patients had normal plasminogen activator inhibitor-1 levels. Blood Coag Fibrinol 9:167–171 × 1998 Lippincott-Raven Publishers.