Transforming growth factor (TGF)-betas are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-beta action in the context of the whole animal. Overexpression of TGF-beta can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-beta function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-beta response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-betas have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-beta receptors seen in some human breast hyperplasias may play a causal role in tumor development.