The aim of this work was to examine the role of prolactin and dopaminergic drugs, which affect prolactin secretion, on proliferative and morphogenetic reactions in the uterus under continuous estrogen treatment. Ovariectomized mice received injections of estradiol dipropionate (2 microg per 100 g, weekly) or vehicle and daily injections of prolactin (0.25 mg/100 g) or saline (0.05 ml) for 30 days. Other groups of mice received injections of estradiol or vehicle and injections of saline, and were allowed to drink bromocriptine (25 mg/l), metoclopramide (25 mg/l), or only tap water for 30 days. Prolactin administration results in a decrease in the incidence of abnormal glands with abnormal epithelium, the incidence of atypical hyperplasia, uterine weight, proliferation (the number of mitotic and bromodeoxyuridine-labeled cells) and the levels of estrogen receptor-alpha, but causes an increase in the level of beta-catenin in uterine tissues of estrogen-treated mice. The effect of metoclopramide, which increases prolactin secretion, is principally similar to prolactin, but much less expressed. Bromocriptine, which reduces prolactin levels, increases uterine weight, proliferation, the levels of estrogen receptor-alpha, the incidence of abnormal glands with abnormal epithelium, the incidence of complex and atypical hyperplasia, and decreases the level of beta-catenin in uterine structures of estrogen-treated mice. In the absence of estradiol, none of the treatments used had any effect on the parameters tested. Thus, prolactin or metoclopramide produce antiestrogenic effects in the uterus of mice and prevent the formation of atypical hyperplasia which has an unfavorable prognosis, but bromocriptine has the opposite effect. Estrogen receptor-alpha and beta-catenin were associated with the actions of prolactin, metoclopramide and bromocriptine on estrogen-dependent processes in the uterus.