Prostaglandins are considered to participate in the nidation of the embryo. However, so far little is known about the regulation of prostaglandin synthesis in endometrial tissue. In this study, we examined the effect of epidermal growth factor (EGF) on the release of PGE2 with primary cell culture of human endometrium. EGF stimulated PGE2 release dose-dependently in the range between 0.1 ng/ml and 100 ng/ml. PGE2 release was augmented significantly as early as 30 minutes after the addition of EGF, reaching a plateau at 3 hours. The stimulatory effect of EGF was eliminated by the concomitant addition of lipocortin, an inhibitor of phospholipase A2. However, the effect of EGF was not influenced by cycloheximide. Estradiol alone had a weak effect on PGE2 release. However, the stimulatory effect of EGF was more pronounced in cells pretreated with estradiol. In conclusion, this report offers evidence that EGF stimulates the release of PGE2 from human endometrial cells, thus implying the involvement of EGF in implantation.