Two types of hormone-dependent mammary tumors that occur in strain GR/A mice, i.e., those that appear during pregnancy [pregnancy-dependent mammary tumors (PrDT)] and those induced by treatment with progesterone (P) and estrogen (E) [P + E-dependent mammary tumors (P + E-DT)], were compared in terms of serial transplantation, response to pregnancy, and histology. Both types originated as ductal hyperplasias. When the P + E-induced ductal hyperplasias were transplanted into the parenchyma-free mammary fat pad, they displayed behavior similar to that of pregnancy-induced tumors. P + E-induced ductal hyperplasias gave rise to ductal outgrowths in the virgin host and to PrDT in the pregnant host; this evidence indicated that the ductal hyperplasias are preneoplastic lesions in strain GR mice. In a separate study, attempts to induce progression of tumor occurrence toward pregnancy independence were made because no spontaneous progression had occurred after 8-9 serial transplant generations in PrDT lines. In contrast to nontransplanted PrDT, which usually require 3-5 forced breedings of mice to induce pregnancy independence, 6-8 matings were needed to induce progression to pregnancy independence in the transplanted lines. Results suggested that serial transplantation in the cleared fat pad may select for less neoplastic variants.