The specific binding of leukemia inhibitory factor (LIF) or oncostatin-M (OSM) to transmembrane gp190 or gp130 leads to their oligomerization which is necessary for signal transduction. Although, sgp190 and sgp130 counterparts also exist, their biological significance remains to be determined. Interestingly, sgp190 forms have been identified in large amounts in normal mouse sera but so far not in human sera. During gestation, murine sgp190 increases 20-fold to 30-fold, while sgp190 RNA levels increase mostly in the liver, uterus and placenta. Sandwich ELISAs were used to detect the presence and follow the evolution of LIF concentrations and its sgp190 receptor subunit in the sera of healthy pregnant and non-pregnant women. The LIF concentrations in whole blood of pregnant women were significantly lower than those of non-pregnant women, whereas they returned to these latter values soon after delivery. In 51 non-pregnant women, the mean sgp190 concentration was 4.3 0.3 ng/ml. It rose slowly but steadily, increasing 4-fold from the 4th to th 34th week of amenorrhea, at which time, it accelerated more rapidly until reaching 41 weeks of amenorrhea, 12 times the mean control value. Several hours prior to delivery, the sgp190 concentration dropped sharply before returning to control levels 2 days later. The marked increase of sgp190 measured in pregnant women extends to humans the observation previously made in mice and suggests a pivotal role for this cytokine system not only during implantation and early embryo development but also throughout pregnancy and more specifically in the biological function of placenta.