Objectives : To elucidate the mechanisms by which estrogens protect against occlusive vascular disorders, we studied the effect of 17β-estradiol on the production of prostacyclin (PGI 2 ) and nitric oxide (NO) in primary cultures of human umbilical vein endothelial cells (HUVECs). Methods : To study the effect of 17β-estradiol on PGI 2 production, HUVECs were incubated in the absence and presence of 17β-estradiol (0.01–10 nmol/l) encapsulated within β-cyclodextrin for 12 h in serum-free medium. To study the effect of 17β-estradiol (100 nmol/l) on maximal calcium-dependent NO production, we used different approaches. First, HUVECs were incubated with 2 μmol/l calcium ionophore A23187 with or without 17β-estradiol (100 nmol/l) for 24 h in serum-free medium. Second, HUVECs were preincubated with or without 17β-estradiol (100 nmol/l) for 12 h in medium supplemented with 2% fetal calf serum, and thereafter incubated in serum-free medium with 2 μmol/l of A23187 and with 100 nmol/l of 17β-estradiol (cells which contained 17β-estradiol during the preincubation period as well as cells which did not) or without it (only cells which did not contain 17β-estradiol during the preincubation period) for 6 h or 24 h. Results : 17β-Estradiol (0.1 nmol/l) increased the concentration of 6-keto-prostaglandin F 1α , a stable metabolite of PGI 2 in the incubation medium, by 16%, and no further increase occurred with higher 17β-estradiol concentrations. The stimulation was prevented by tamoxifen. 17β-Estradiol did not affect NO production in any of our experiments measured as accumulation of nitrate and nitrite in the experimental medium. Conclusions : The stimulatory effect on PGI 2 production of physiological concentrations of 17β-estradiol, shown now for the first time, may provide one explanation for the ability of 17β-estradiol to protect against occlusive vascular disorders.