AP-2 transciription factors are key regulatrs of mouse embryonic development,Aberrant expression of these genes has also been linked to the progression of human breast cancer. Here, we have investigated the role of the AP-2 geme family in the postnatal maturation of the virgin and pregnant mice. Subsequently, AP-2 expression declines during lactation and then is reactivated during involution. The AP-2α and AP-2γ proteins are localized in the ductal epithlium, as well as in the terminal end buds, suggesting that they may infuence growth of the ductalnetwork. We have tested this hypothesis by targeting AP-2α expression to the mouse mammary gland using the MMTV promoter. Ourstudies indicate that overexpresion of AP-2α inhibits mammary gland growth and morphogenesis, and this coincides with a rise in PTHrP expression. Alveolar buding is severly curtailed in transgenic virgin mice, while lobuloalveolar development and functional differentiation are inhibited druing preganancy and lactation, repectiely. Our studies strongly support a role for the AP-2 proteins in regulating the proliferation and differenatation of mammary gland epithelial cells in both mouse and human.