In vivo studies suggest that 17 beta-estradiol (beta E) may regulate vascular tone. Results of recent studies suggest that beta E exerts rapid effects on intracellular calcium, possibly via cell surface receptors, distinct from conventional nuclear receptors for steroids. The present study was designed to determine whether beta E acutely modifies vascular smooth muscle contractile responses to phenylephrine (PE) and angiotensin II (AII). In experiments on tonic responses of aortic rings to 5 x 10(-8) mol/L PE, cumulative additions of beta E reduced tension at concentrations > 10(-6) mol/L. Contractile dose responses to PE were determined in rat aortic rings in absence of sex hormones and then after exposure to beta E (5 x 10(-6) mol/L, n = 6) or vehicle (ETOH, n = 6) for 30 min. beta E increased ED50 and reduced maximal responses. Application of 5 x 10(-6) mol/L beta E for 30 min also reduced the contractile response to 1 mmol/L AII from 69 +/- 4% (vehicle) to 47 +/- 6% (estradiol) of maximal KCl contraction (P < .025, n = 7). These data suggest that beta E acutely attenuates vasoconstrictor responses to PE as well as to AII, possibly by an effect exerted at the cell membrane level.