Blastocyst implantation and maintenance of pregnancy involve a series of events involving endocrine and paracrine factors. In particular, hormones and cytokines appear to be very important in creating the environment essential for placenta establishment. In this study we investigated the effect of 17b-Estradiol (E2) on the secretion of the Macrophage Migration Inhibitory Factor (MIF), a pro-inflammatory cytokine highly involved in the early stages of pregnancy. By using the HTR8/SVneo cells we performed dose-response experiments with E2 concentrations ranging from 10^-15 to 10^-5M. We found that 10^-10 and 10^-13M E2 were the highest and the lowest concentrations having significant effect respectively reducing and increasing MIF levels in the culture media. Treatment with ER antagonists ICI 182 780 restored MIF levels in E2-treated samples to those of controls. These findings support interaction between hormones and cytokines in human trophoblast cells and show that MIF release is hormone receptor-dependent.