The normal development of the breast, as well as the risk of developing breast cancer, are strongly dependent on endocrine conditions modulated by the ovary. Beatson demonstrated as early as 1896 (Russo et al., J. Mam. Gland Biology Neoplasia 3:49, 1998) that breast cancer is an ovarian and, therefore, hormone-dependent malignancy, since removal of the ovaries caused regression of disseminated breast cancer. Over the years numerous additional factors have been discovered to modify the risk of developing breast cancer. Increased risk has been associated with family history of breast or breast/ovarian cancer, nulliparity, late first full term pregnancy, early menarche, late menopause, exposure to ionizing radiation at young age, and high socioeconomic status. Although the cause and the time of initiation of the carcinogenic process are not known, epidemiological, clinical, and experimental data have identified the period between menarche and the first full term pregnancy as a "window" of critical importance for the lifetime risk of developing breast cancer. The narrowing of this "window" that occurs with late menarche and early full term pregnancy confers protection. The fact that breast cancer risk increases when this "window" is widened, such as it occurs in early menarche, late full term pregnancy or nulliparity, suggests that this period is one of maximal susceptibility of the breast to be damaged by known or still unidentified noxious agents. This postulate is supported by the increased breast cancer incidence reported in women that were exposed to ionizing radiations during such a period. Understanding the complex interactions involved in the initiation and progression of breast cancer requires the design of studies in which these variables can be carefully controlled. Experimental animal models provide the ideal conditions for exploring the role of chemicals and hormones on the risk of mammary cancer development. We have designed studies with the purpose of clarifying the mechanisms mediating the protective effect of pregnancy on breast cancer development utilizing the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) for inducing mammary cancer in rats. Our results led us to conclude that the effect is purely hormonal, since the same degree of protection can be induced by treatment of virgin rats with one of the hormones produced during pregnancy, chorionic gonadotropin (CG). This treatment inhibits both the initiation and progression of chemically induced mammary carcinomas. Understanding the ultimate mechanism of action of human CG (hCG) is essential for fully utilizing the potential of this hormone in breast cancer treatment and prevention.