Abstract. Although the biological role for whey acidic protein (WAP) in milk has been suggested, its true function is not known. This paper describes evidence for WAP function in the cell-cycle progression of EpH4/K6 (EpH4), mammary epithelial cells in vitro. The forced expression of exogenous WAP significantly impaired the proliferation of EpH4 cells, whereas it did not affect that of . Recently, it has also isolated from the milk of pigs [5,6], and three marsupial species, tamer wallaby [7], red kangaroo [8], and brushtail possum [9]. Expression of the WAP gene is regulated by lactogenic hormones, and the level of mo use WAP m RN A in the m am m ary gla nds incr eases t hous ands -fo ld between non-lactation and mid-lactation [10]. WAP proteins have a signal peptide [11] and two domain structures that are identified at the fourdisulfide core (4-DSC) domain, which is composed o f ei g h t c y s t ei n e r es id ue s i n a c o ns er v ed arrangement [12]. The 4-DSC domain arrangement is not exclusive to the WAP family, and a number of other proteins containing 4-DSC domains have been identified as protease inhibitors [11,[13][14][15][16], comprising either single or multiple copies of the 4-DSC domain. Generally, these proteins are secreted and may function as protease inhibitors [17,18]. Thus, based on the limited sequence identity with a known protease inhibitor, it has been postulated that WAP may be a secreting protease inhibitor [18,19], and its biological function has been suggested.