The heparin-antagonizing effect of human α1-acid glycoprotein (α1-acid GP) was studied by activated partial thromboplastin time (APTT) and by a factor Xa assay for heparin using a chromogenic substrate for factor Xa. The antiheparin effect of α1-acid GP in the APTT system was similar to the effect on heparin thrombin clotting time (HTCT), and the effect in the factor Xa assay system corresponded well with the effect in a heparin cofactor assay system using a chromogenic substrate for thrombin instead of factor Xa. It is concluded that α1-acid GP contributes to the reduced anticoagulant effect of heparin observed in various acute stages of disease, when assayed not only by HTCT but also by so-called ‘global’ coagulation tests, such as the activated partial thromboplast