Tamoxifen (TAM) has been shown to induce apoptosis in breast cancer cells. bcl-2 family genes, which can interact with each other, have been shown to interfere with apoptosis after various stimuli. In this study, we investigated the effects of TAM on bcl-2 family gene products bcl-2, bax, and bcl-X(L) and on p53 levels in estrogen receptor-positive MCF-7 breast cancer cells. We found that TAM induced time- and concentration-dependent down-regulation of bcl-2 at both the mRNA and protein level. Down-regulation of bcl-2 correlated with TAM-induced apoptosis. In addition, estradiol treatment significantly increased bcl-2 protein expression and blocked the reduction of bcl-2 by TAM. TAM did not, however, affect bax, bcl-X(L), or p53 expression at the mRNA or protein level. Our results demonstrate that TAM can induce apoptosis in a time- and dose-dependent manner by modulating bcl-2 levels in breast cancer cells, and down-regulation of bcl-2 induced by TAM was not accompanied by alterations in p53 levels.