Human interleukin for DA cells, also called leukaemia inhibitory factor (LIF), is of cardinal importance for successful murine embryo implantation. Recent studies suggest it may also play an important role in human embryo implantation. Our objective was to study the hormonal regulation of the production/secretion of LIF by the human endometrium. Endometrial LIF secretion in specimens obtained from women without ovarian function (n+/-14) at day 10 (4 mg of oestradiol regimen) or day 20 (oestradiol plus 300 mg of progesterone) of a simulated menstrual cycle was examined. LIF was detected in all cultured explants obtained both in the proliferative and secretory phase of the stimulated cycles. The levels of cytokine production by day 10 endometrial culture explants were 5-fold higher than by day 20 endometrial samples (mean+/-SEM, 24.3+/-8.6 versus 4.5+/-2.1 pg/mg, P < 0.01). This suggests that progesterone significantly down-regulates the endometrial LIF secretion. The effect of progesterone on LIF secretion by the endometrium in vitro was also examined. Explants of endometrium obtained from the same patients on day 10 of cycle were treated with 0.5 ng/ml of progesterone in vitro. This progesterone treatment significantly reduced LIF secretion by endometrial explants in vitro (mean+/-SEM, 20.3+/-4.8 versus 10.7+/-2.3 pg/mg, P < 0.05). These results suggest that LIF endometrial production is regulated by progesterone both in-vivo and in-vitro. The possible mechanisms of LIF regulation are discussed briefly.