OBJECTIVE To determine whether primitive endothelial precursor cells are present in the peripheral blood of pregnant compared with nonpregnant subjects and whether these precursor cells are of fetal or maternal origin. METHODS Peripheral blood mononuclear cells from 13 pregnant women in the second trimester and from ten nonpregnant women and men were cultured for 8-10 weeks under conditions that promoted endothelial cell development. Early outgrowth (1 week culture) and late outgrowth (4-6 weeks) colonies were observed, their endothelial nature was investigated, and fluorescence in situ hybridization was performed to determine the origin of the colonies from pregnant women's specimens. RESULTS Peripheral blood mononuclear cell cultures from all pregnant women and all nonpregnant controls yielded early-outgrowth endothelial cells. Late-outgrowth endothelial cells were observed in 61.5% (eight of 13) of pregnant subjects, but in none of the ten nonpregnant controls (chi(2) test; P <.01). The adherent cells stained positively for von Willebrand factor and incorporated Dil-Ac-LDL, confirming their endothelial origin. Fluorescence in situ hybridization analysis showed only X chromosome-specific signals and no Y chromosome-specific signals in the cells from the late-outgrowth endothelial cells in all pregnant women carrying either a male (n = 5) or a female (n = 8) fetus. CONCLUSIONS Primitive endothelial precursor cells are present in most pregnant women during the second trimester. These cells appear to be of maternal origin.