Annexins (Anx) are a family of structurally related proteins that all bind to anionic phospholipids in a Ca(2+)-dependent manner. Some biological properties of beta-2-glycoprotein I (beta(2)-GPI) are similar to those of Anx IV and Anx V. Urinary trypsin inhibitor (UTI) helps to maintain normal pregnancy and prevent preterm delivery by inhibiting uterine contraction. However, plasma beta(2)-GPI and UTI levels have not been measured in normal pregnancy. The aim of this study is to clarify the levels of these parameters. Subjects were nonpregnant women (n=50), 120 pregnant women, and maternal subjects just after delivery (n=53) or postpartum (n=67). All of the subjects were healthy. Plasma levels of beta(2)-GPI, UTI, Anx IV, Anx V and other coagulation and fibrinolysis markers were measured by ELISA. The mean plasma level of beta(2)-GPI was significantly increased during the third trimester of pregnancy and 3 to 5 days after delivery. The mean plasma level of UTI was unchanged from the first trimester of pregnancy to the postpartum period. The mean plasma UTI level in vaginal delivery group was significantly higher than that in cesarean section group. beta(2)-GPI protein was expressed in some of the syncytiotrophoblasts. These data suggest that beta(2)-GPI might act to prevent blood clotting on the placental surfaces and also prevents disseminated intravascular coagulation in the microcirculation and maternal plasma. UTI levels might be kept constant by increased urinary excretion despite overproduction during pregnancy.