β-HCH is known to be a poor agonist for the estrogen receptor (ER), and yet it has been shown to act like an estrogen in stimulating foci formation in MCF-7 cells. We investigated the reason for such an action of β-HCH, using a rat prolactin-luciferase reporter system transfected to MCF-7 cells. We found that the presence of c-Neu (erbB2), ER and ERE is needed for β-HCH to act estrogenic at the transcription activation level in this cell line. We compared the action of β-HCH to that of EGF which is known to act estrogenic without being an agonist for ER in this cell and found that their action patterns are quite similar, the only difference being that the former action is blocked by an antibody against c-Neu and the latter by both c-Neu and EGF receptor antibody. We concluded that β-HCH's estrogenic action in this cell model is mediated through "ligand-independent activation of ER pathway".