The directed expression of SV40 Tag to mammary epithelial cells by the rat hormone-responsive C3(1) 5Õ flanking region leads to the development of mammary adenocarcinomas in 100% of females and death by 6 months of age. Tumors arise primarily from ductal cells where hyperplastic foci are first seen as early as 2 months of age and progress to invasive carcinomas over several months. Mammary tumor progression in this model does not appear to be highly estrogen dependent, as mice ovariectomized at three weeks of age develop mammary tumors with similar frequency and time of onset as control transgenic mice. Animals which become pregnant shortly after the appearance of the first mammary tumor nodule appear to demonstrate a significant delay in the development of additional mammary tumor foci, although existing tumors appear to shown accelerated growth as measured by tumor volume. Histopathological analyses reveal that the majority of early hyperplastic lesions regress during pregnancy, whereas existing carcinomas continue to grow during pregnancy. These phenomena correlate with the expression of Tag. We conclude that in C3(1)/Tag transgenic mice: 1) preneoplastic mammary lesions are reversible during pregnancy; 2) existing mammary tumors appear more aggressive during pregnancy. This transgenic model may be useful for understanding how pregnancy reduces the risk of developing breast cancer in humans and why breast cancer diagnosed during pregnancy is often more aggressive than that observed in non-pregnant women. Possible mechanisms to explain these results will be presented.