During our research programme on implantation failures after in-vitro fertilization (IVF), we investigated the expression of leukaemia inhibitory factor (LIF) by endometrial cells in women who have experienced several implantation failures after embryo transfer. Their embryos appeared to be morphologically normal and were either fresh or cryopreserved. Our intention was to investigate the role of LIF in regulating human preimplantation embryo development. In animals, the addition of 1000 IU/ml of recombinant human LIF (rhLIF) to culture medium, in comparison with control medium, significantly decreased the degeneration of ovine embryos (9 versus 27%), enhanced embryo hatching (64 versus 16%), and improved rates of implantation (50 versus 16%) (Fry et at., 1992). In the same way, co-culture cells that express LIF (including Vero cells and human embryonic fibroblasts) seemed to be superior to cells that did not express LIF (including human placental villous core mesenchymal cells) for the support of the early preimplantation development of mouse embryos (83-86% blastocysts versus 71 %) (Kauma and Matt, 1995). In our study, we first assessed LIF expression in endometrial cells by taking three uterine biopsies in one natural cycle in a group of women. Biopsies were taken in the luteal phase, i.e. early (2-4 days after ovulation), mid (6-7 days) and late (10-l2 days). LIF expression was checked by immunocytochemistry using double labelling with both anti-cytokeratin antibodies (fluorescein) and anti-LIF antibodies (rhodamine). Three observations were made: (i) endometrial cells (epithelial and stromal) contained LIF immunoreactivity in the luteal phase (3-11 days after ovulation); (ii) labelling was more intense for epithelial than stromal cells, indicating that differences existed in their LIF secretion; (iii) labelling was stable during the luteal phase in epithelial cells whereas it increased in stromal cells during the luteal phase. In a second experiment, embryo co-culture was performed on endometrial cell monolayers. The endometrial cells were obtained from biopsies carried out 3 days after ovulation in the preceding menstrual cycle; 5 days after beginning co culture, blastocysts were transferred into the uterus of patients and the conditioned media from the embryo cultures were assayed for LIF secretion. The endometrial