After intravenous and subcutaneous injection, heparins and low-molecular-weight heparins release tissue factor pathway inhibitor (TFPI) into the blood stream. Protamine immediately reverses the plasma levels of TFPI to pretreatment values. A low-molecular-weight dermatan sulphate releases only very small amounts of TFPI after intravenous injection without a clear dose-dependent effect. Together with other data from literature, it seems likely that TFPI is rather specifically released by acidic glycosaminoglycans. In the present paper a binding region for heparins is reported to be located in the C-terminal end. A basic amino acid cluster occurs between 256-lysine and 261-lysine. This proposed heparin recognition region in TFPI is similar to the recognition region in antithrombin III and other proteins. The binding between the basic region at the C-terminal end of TFPI and the negatively charged sulphate or carboxyl-groups of glycosaminoclycans may occur in a linear manner. A comparison of a helical wheel diagram of antithrombin III and tissue factor pathway inhibitor support also the proposal of this form of a heparin recognition region in TFPI. Further studies are now required to analyse these interactions.