2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent inducer of differentiation and an antiestrogen, is shown to suppress in vitro postconfluent cell accumulation in the estrogen-dependent MCF-7 human breast tumor cell line. This dose-responsive suppression is apparent by 14 days of exposure with an EC50 between 10(-10) and 10(-11) M TCDD, and is characterized by reduced cell density (approximately 60% of controls after 14 days). This was attributed to a reduced formation in TCDD-treated cultures of multicellular foci which are characteristic of cancer cell growth in vitro (less than 1/mm2 compared to control levels of 40/mm2). Preconfluent cell growth and viability of MCF-7 cells is not affected by 10(-9) M TCDD. These results suggest that the principle of TCDD's activity may be useful in the study and possibly the management of estrogen-dependent breast tumors.