Thrombo-embolic disorders are so far one of the most frequent causes of death in developed nations. Therefore, the improvement of their prophylaxis and therapy as well as the further elucidation of their etiology and pathogenesis are important tasks of national health programmes of developed countries. The objective of the present study is to investigate the effect of polyanionic compounds on blood coagulation and individual blood coagulation components in vitro. Among the twelve substances tested are two recently synthesised sulphated hyaluronic acids, two natural humic acids (HA) of different origin (peat water and brown coal, respectively), six synthetic humic acid-like polymers and two anticoagulant agents in therapeutic use (heparin and pentosan polysulphate). Methods: The influence of the test substances on blood coagulation and the blood coagulation factors IIa, Xa (in the presence and in the absence of antithrombin III) and VIIa as well as on the protein C anticoagulant pathway is evaluated by clotting time measurements and by determining amidolytic activities (IIa, Xa, activated protein C) using chromogenic substrates. Results: A concentration-dependent anticoagulative effect neutralizable by protamine sulphate could be found for all test substances in human plasma. With the exception of heparin, test substances did not need any cofactor for their anticoagulatory activity. The sulphated hyaluronic acids proved to be most active in both the prolongation of coagulation time and the inhibition of factors IIa, Xa and VIIa. They represent a new type of anticoagulatory active substances, which in comparison to heparin possess several benefits relating to production, pharmacological profile and pharmacokinetics. Among the HA-like polymers, the melanoidin M42 prepared from glutaminic acid and xylose and the oxidation product of caffeic acid (KOP 409/85) proved to be most effective. The anticoagulative effect of the polyanions is based on the inhibition of the coagulation factors IIa and Xa, which depends, in the case of hyaluronic acids, on molecular weight and sulphatation degree, in the case of natural HA, on the type of origin. All test substances were able to prolong the extrinsically activated coagulation by inhibition of FVIIa. Activated protein C was only marginally influenced. Altogether, the natural HA investigated in this study provide mainly anticoagulant and profibrinolytic properties. In that they are different from the so-called "fluorescent HA" occurring in Taiwanese artesian well water and are suspected of causing Blackfoot disease, an endemic peripheral vascular disease in man.