It has been established that serum soluble endoglin (sEng) increases in women with preeclampsia. However, sEng levels have not been evaluated using a normal reference value specific to each gestational age. First, we established the normal reference value for sEng using 85 pregnant controls without preeclampsia, from whom serum samples were collected three times at 20-23, 27-30, and 36-38 weeks of gestation. Second, we evaluated the serum sEng levels after the onset of preeclampsia in 56 preeclamptic patients. In three women (3.5%) with normal pregnancies, sustained high sEng levels (>15 ng/mL) were observed. We calculated the reference value for sEng using the remaining 82 normal controls. The log10sEng was almost normally distributed at each gestational week during 20-38 weeks, and the mean log10sEng was represented as a quadratic curve of gestational week. The SD of log10sEng was represented as a linear equation of gestational week. The mean log10sEng significantly and gradually increased from 20-23 weeks to 27-30 weeks of gestation and then rapidly increased at 36-38 weeks of gestation. Ninety-three percent of preeclamptic women showed sEng>or=95th percentile of the reference value. The log10sEng levels and the SD score (SDS) of log10sEng in women with early-onset preeclampsia (onset<32 weeks of gestation) were significantly higher than those in women with late-onset preeclampsia (onset>or=32 weeks of gestation) (1.97+/-0.23 vs. 1.78+/-0.28, 9.94+/-2.61 vs. 4.47+/-2.06, respectively). In conclusion, alteration of serum sEng levels after the onset of preeclampsia was more pronounced in women with early-onset preeclampsia compared to those with late onset.