Although estrogen has been reported to relax large coronary arteries immediately, its direct acute effect on small vessel tone has not been fully defined. In this study, we investigated the effect of estradiol-17beta and progesterone on isolated rat saphenous artery segments-with an internal radius of 250 microm-by measuring the outer diameter of the vessels using in vitro angiometry. Estradiol and progesterone at concentrations of 1-100 and 8.6-86 microM induced a rapid, dose-dependent relaxation of the arterial segments precontracted with norepinephrine. Maximal changes of diameters were 85.8 +/- 10 and 90.9 +/- 8%. Clomiphene citrate, a cytoplasmic receptor antagonist, did not diminish this action of estradiol, with the exception of the highest concentrations of the hormone. Thus a nongenomic pathway for this effect can be suspected. Dexamethasone did not induce similar vasodilation. It is concluded that estradiol and progesterone have similar rapid vasorelaxing effects on small muscular arteries as found previously on coronary arteries.