Tamoxifen [an antitumor agent] and nafoxidine compete specifically with estradiol for the estrogen receptor in the fetal uterus of the guinea pig. [3H]tamoxifen binds to the cytosol macromolecules of this fetal tissue at 2 classes of binding sites, one with a dissociation constant (Kd) of 1.8 .+-. 0.4 .times. 10-9 M and a concentration of specific binding sites (n) of 1800 .+-. 100 f[femto]mol/mg protein, which corresponds to the same specific binding site as does estradiol, and a 2nd class of sites with a Kd of 3.9 .+-. 0.1 .times. 10-10 M (617 .+-. 77 fmol/mg protein), which does not bind estrogens. Tamoxifen or nafoxidine injected into the mother (1 mg/kg per day for 3 consecutive days) stimulates fetal uterine weight with an intensity similar to that of estradiol but, in contrast to estradiol, the stimulatory effect of the progesterone receptor is limited. Estradiol decreases by 80% the total number of specific estradiol binding sites (cytoplasmic plus nuclear). Tamoxifen and nafoxidine can translocate the estrogen receptors into the nucleus, but they have only a limited effect on the total number of specific binding sites of estradiol. The fetal uterus of the guinea pig apparently responds to the effect of estrogens and antiestrogens.