The effect of estrogen stimulation in vitro on the electrical properties of vascular smooth muscle (VSM), and the concentration of estrogen receptors in VSM were measured in isolated coronary arteries. Microelectrode measurements of the dog coronary artery membrane potential (Em) showed quiescent values of -51 millivolts (mV) and an input resistance kin) of 10 megohms. Addition of diethylstilbestrol (DES) a t M hyperpolarized the membrane to -64 mV and reduced input resistance (Tin) to 5 megohms within 15 minutes. Extrapolation of the Em vs. log [Kl0 curve to zero potential gave similar values of [Kli of around 170 mM in both normal and DES treated muscles suggesting that the DES induced hyperpolarization is not due to increased Na-K pump activity. The 0.5% ethanol vehicle alone had no effect on the membrane potentials. Tetraethylammonium ion (TEA) induced action potentials in the previously quiescent tissue. When DES was applied in the presence of TEA, the membrane potential increased and the action potentials were abolished. Scatchard analysis of the estrogen receptor binding demonstrated both a high and a low affinity receptor for estrogen in the VSM. These data indicate that DES hyperpolarizes the VSM cells by a mechanism other than an increased Na-K pump activity. The mechanism of this increased Em may be due to factors which increase K' conductance either mediated directly through estrogen interaction with its cytosolic receptors or through some unidentified second mechanism Infusion of estrogens has been demonstrated to increase blood flow in certain vascular beds of man, sheep, rats and other animal species (Altura and Altura, '77a,b). Addition of estradiol-17-/3 to isolated rat portal vein inhibits spontaneous contractions (McCalden, '75). However, other reports have indicated that estrogens may maintain or enhance vascular tone in cerebral arteries of adult women (Gabrielson and Grietz, '70). The mechanisms responsible for the effects of estrogen on vascular smooth muscle (VSM) are not well understood, nor has the existence of receptors for estrogens in VSM been demonstrated. Study of the direct effects of estrogens on VSM is complicated by the findings that the responsiveness of blood vessels to other vasoactive agents (e.g., angiotensin, epinephrine, serotonin) are enhanced by their presence (Altura and Altura, '77b). The effects of estrogens on