PIP: A preliminary isolation of an estrogen specific binding macromolecule from the human uterus is described. Tritiated-estradiol-17beta was incubated with uterine cytosol fractions (273,000 g supernatant) and various nonradioactive steroids. Sucrose gradient centrifugation was employed in isolating the human estrogen, and bound steroids were separated from the unbound by dextran-coated charcoal. Only nonlabeled estrogens depressed the quantity of bound estradiol. Ethynyl estradiol, estriol, and estradiol-17beta competitively inhibited tritiated-estradiol binding, whereas, cholesterol, cortisol, testosterone, progesterone, and norethindrone did not. Sucrose density gradient ultracentrifugation also revealed binding of estradiol to uterine cytosol. It is concluded that these data sugges t the presence of an estrogen-binding macromolecule in the human uterus similar to that in lower mammals making various hormone receptor studies applicable to both man and mammals.