The Copenhagen (COP) rat is unique among inbred rat strains in its high degree of resistance to spontaneously arising and induced mammary cancers. Hyperprolactinemia resulting from tumors of the anterior pituitary gland has been suggested to be the causative factor in the etiology of estrogen-induced mammary cancer in rats. Therefore, we have examined the ability of administered estrogens to induce development of PRL-producing pituitary tumors and mammary carcinomas in COP rats. Diethylstilbestrol (DES), administered to male COP rats for 12 weeks, beginning when the animals were 9 weeks of age, induced development of PRL-producing pituitary tumors, defined as grossly enlarged pituitary masses displaying lactotroph hyperplasia and associated hyperprolactinemia. When treated with 17beta-estradiol (E2), female COP rats developed pituitary tumors and hyperprolactinemia, but displayed a high degree of resistance to development of mammary carcinomas. These data indicate that E2-induced hyperprolactinemia is insufficient to induce development of mammary carcinomas in the female COP rat.