Although the physiological role of beta(2)-glycoprotein I (B(2)GPI) is unknown, in vitro evidence indicates that B(2)GPI may be a natural anticoagulant. In this study we have examined whether fluctuations of plasma B(2)GPI occur in in vivo coagulation. Serial measurements of B(2)GPI and other anticoagulant proteins were performed in 51 patients with thrombotic (group 1: six patients with disseminated intravascular coagulation (DIC), group 2: venous (n=4) or arterial (n=17) thrombosis) and non-thrombotic disease (group 3: 24 patients undergoing elective surgery). Reductions in plasma B(2)GPI levels were seen in most patients which were roughly proportional to the severity of their illness. Particularly striking reductions of B(2)GPI, protein C (PC) and antithrombin III (AT-III) (mean +/- 95% CI: 42.7 +/- 8.6%, 42.1 +/- 14.8%, 39.1 +/- 28.4% respectively) were seen in group 1. The reductions in plasma B(2)GPI were significantly greater in group 1 than in the other groups. Dilutional factors explain most of the reductions in B(2)GPI, PC and AT-III in groups 2 and 3, but contribute little to group 1. In conclusion, although B(2)GPI behaves as a 'negative acute phase reactant', the magnitude of reduction of plasma B(2)GPI levels, accompanied by reductions in other anticoagulant proteins in patients with DIC, suggests specific consumption of B(2)GPI in in vivo coagulation. This study provides further evidence that B(2)GPI is an anticoagulant of physiological importance.