Epidermal growth factor stimulates prostaglandin production and cyclooxygenase activity in endometrial stromal cells isolated from the uteri of ovariectomized rats sensitized for the decidual reaction. The present study examined the effect of epidermal growth factor on cyclooxygenase-1 and cyclooxygenase-2 mRNA and protein levels in these cells. Treatment with epidermal growth factor (40 ng/ml) for 24 hr increased steady-state cyclooxygenase-1 and cyclooxygenase-2 mRNA and protein levels in the cells as determined by Northern and Western analyses. Dexamethasone inhibited the epidermal growth factor-induced increased in steady-state mRNA levels fro cyclooxygenase-2, but not for cyclooxygenase-1. Finally, the effects of epidermal growth factor and dexamethasone on steady-state cyclooxygenase-1 and cyclooxygenase-2 mRNA levels paralleled the changes in the levels of immunocytochemical staining for these enzymes in the cells. This showed that the changes in cyclooxygenase-1 and -2 protein levels were due to generalized changes in most cells, and not to changes in a subpopulation of stromal cells. The results of this study suggest that epidermal growth factor causes an increase in cyclooxygenase-1 and cyclooxygenase-2 gene expression in endometrial stromal cells isolated from the uteri of rats which have been sensitized for decidualization, and that the previously reported transcriptional- and translational-dependent increases in cyclooxygenase activity in these cells in response to epidermal growth factor were likely due to its effect on cyclooxygenase-1.