According to a novel mechanism for fetal evasion from maternal immune attack via the engagement and down-regulation of the maternal natural killer cell receptor NKG2D by soluble MHC class I chain-related proteins (sMIC) A and B derived from placenta, we aimed to measure whether the sMICA/B level altered during pregnancy.Healthy women undergoing routine antepartum examination at Kee-Lung Chang Gung Memorial Hospital from December 2006 to December 2007 were prospectively registered for this study.We collected 337 serum specimens and 10 amniotic fluid samples from 300 normal pregnant women for sMICA/B analysis.Capture ELISA procedures were used to determine sMICA/B concentration in serum and amniotic fluid specimens.We hypothesized that the sMICA/B level would increase in proportion to the gestational age to protect the fetus from maternal immune rejection in the normal pregnancy. Results. The serum sMICA/B level rose gradually with the progression of gestation and decreased after the second trimester, with the lowest level appearing before delivery. In addition, we found that levels of soluble MICA/B were extremely low in amniotic fluid.We suggest that, as delivery approaches, the reduced production of soluble MICA/B by the aged placenta may be playing a role in parturition. Furthermore, we suggest that the effect of soluble MICA/B on natural killer cells of pregnant women is limited to the maternal placental surface, but not transferred through the placenta into the amniotic cavity.