Cardiovascular effects of estrogens have been shown to be of great clinical importance treating patients with hormonal replacement therapy or using oral contraceptives. To test one nongenomic mechanism of direct vascular action, the calcium-antagonistic effect of natural and synthetic estrogens was investigated in cell cultures of human vascular muscle cells. 17 beta-estradiol significantly inhibited calcium influx at the concentrations of 10(-6) and 10(-7) M in resting and activated cells. Neither the natural estrogens, estrone, and estriol nor the synthetic estrogens, 17 alpha-estradiol and 17 alpha-ethinylestradiol, significantly changed calcium homeostasis in these cells. The results suggest that the vasodilatory effect of 17 beta-estradiol, seen with hormone substitution in postmenopausal women, could be mediated at least partly via influence on calcium homeostasis.