The effects of P and six synthetic steroids (MPA, ENT, CAP, R2323, DL and EEL) on estradiol dehydrogenase (E2DH) activity were studied in normal human uterine endometrium in vitro. The mean value of E2DH activity in the proliferative endometrium was 1.5 +/- 0.2 nmol/mg protein/h and that in the secretory endometrium was 10.2 +/- 1.1 nmol/mg protein/h. There was a 7-fold increase in the secretory phase. E2DH activity in the uterine endometrium was stable during the culture period of up to 72 h. In the proliferative endometrium, P, MPA and ENT (approximately 10(-6)M) induced E2DH activity during a 24-h incubation. CAP and R2323 had no significant effect. EEL and DL had negligible effects. In contrast, E2DH activity in the secretory endometrium was not induced further by the steroids. Therefore, in the proliferative endometrium, the elevation of E2DH activity is attributable to the progestational activity and, in the secretory endometrium, E2DH activity is not increased further by the progestational agents because it has been already activated fully by P.