beta 2 glycoprotein-I (beta 2 GPI) is a 50 kDa plasma protein which associates with a number of anionic plasma constituents and has been identified as a cofactor for the binding of some antiphospholipid antibodies (aPAs). beta 2 GPI antigen levels are increased in some patients with aPAs. In order to examine the distribution of beta 2 GPI in these patients, we developed a method for measurement of free beta 2 GPI. Forty-three patients with SLE, of whom 18 had laboratory evidence of aPAs, and 22 normal healthy subjects were studied. Plasma was filtered by centrifugation at 650 x g through a 100 kDa filter in order to allow separation of free and complexed beta 2 GPI, and beta 2 GPI levels were measured in the starting plasma and filtrate by a standardized ELISA. Total beta 2 GPI levels of the SLE aPA positive patients (253.3 mg/l) were significantly increased compared with the SLE aPA negative patients and normal controls (188.0, P < 0.001 and 194.9 mg/l, P < 0.01, respectively), but there were no significant differences between free beta 2 GPI levels of these groups (20.8, 24.0 and 20.5 mg/l, respectively). These results suggest that levels of complexed beta 2 GPI are increased in patients with aPAs, perhaps as a result of immune complex formation, or altered binding to other plasma constituents.