Progesterone is known to stimulate cell proliferation of normal and neoplastic rodent mammary tissues. Recently we have observed that while progesterone is highly effective in sexually mature mice, no significant effect of progesterone can be demonstrated in immature, pubertal mammary gland. In the case of the adult gland, the mitogenic effects of progesterone appear to be related to the presence of E-dependent progesterone receptors (PgR). By contrast, immature mammary glands lack E-dependent PgR. The purpose of the present studies was to study the ontogeny of E-dependent PgR and the factors that lead to the acquisition of responsiveness to progesterone. The results obtained demonstrate that E-dependent PgR are first detectable at 7 weeks of age. Analysis of changes occurring in the mammary gland around this time indicate that E-dependent PgR are not acquired until the pubertal mammary epithelial growth phase has occurred. Furthermore both the growth phase and acquisition of PgR are dependent upon the presence of the ovaries. Analysis of concentration and subcellular distribution of both PgR and estrogen receptors indicate that there are no differences between pubertal and adult mice that could account for the absence of this estrogenic response and lack of E-dependent PgR in immature mammary gland.