Recent studies have suggested that epidermal growth factor (EGF) and plasminogen activators (PA) are involved in the implantation of concepti. Therefore we attempted to evaluate the effect of EGF on the release of PA in primary cultures of human endometrial cells. The addition of EGF to culture medium increased the release of tissue-type PA (t-PA). The effect of EGF was significant at 5 ng/ml, which produced a 45% increase in t-PA release. EGF also stimulated the release of urokinase-type PA (u-PA), as well as the release of PA inhibitor type 1 (PAI-1). These stimulatory effects on the release of t-PA and PAI-1, but not of u-PA, were enhanced by the concomitant addition of progesterone. The modulatory effect of EGF on PA release seemed to be selective in that other growth factors, such as basic fibroblast growth factor, transforming growth factor β and interleukin-1β, did not affect the release of PA. From these data, we propose that EGF in concert with progesterone participates in embryo implantation, the process entailing tissue remodelling and cell migration in part by modulating the PA/plasmin system.