Toxaphene is the most abundant persistent organic pollutant in the Arctic and in the Great Lakes. Toxaphene technical mixture (Tox) applied as a pesticide consists of over 800 congeners. Through processes of environmental degradation, selected metabolism, and bioaccumulation, two congeners are prominent in humans; 2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane (T2 or Parlar 26) and 2-exo,3-endo,5-exo,6-endo,8,8,9,10, 10-nonachlorocamphene (T12 or Parlar 50). The MCF7-E3 human breast cancer cell model was used to screen for the estrogenic activities of Tox, T2, and T12. A concentration of 10 microM was required by all three compounds to elicit an estrogenic response as indicated by a proliferative effect (PE) upon the cells. The congeners, however, showed significantly different PEs from Tox. Both T2 and T12 had a lower PE (16 and 30%) and than Tox, and T2 had a higher PE than T12 (19%). Results from binary combination studies showed that the effects of Tox, T2, and T12 were additive. Tox, T2, and T12 had no significant effects on estrogen receptor and progesterone receptor levels. Our results suggest that the two environmental prevalent congeners had lower estrogenic activities than Tox and there is no synergistic effect.