We studied the morphological changes induced by 17-b-estradiol (E2) and/or Epidermal Growth Factor (EGF) in an estrogen sensitive human breast cancer cell line (CG5) characterized by a high growth responsiveness to EGF and by a single class of high affinity I-125 EGF binding sites. EGF treated cultures showed conspicuous morphological changes consisting of retraction from the substrate, loss of cell-to-cell contacts and expression of surface crest-like and bled protrusions. E2-treated cells showed an increased number of microvilli with respect to control. In cells simultaneously treated with EGF and E2, despite the expression of microvilli, cell surface modifications were similar to those found in the presence of EGF alone, suggesting that EGF may negatively modulate the estrogen-induced morphological changes. In CG5 cells EGF induced a reduction of ER and PR levels and inhibited the estrogen-induced increase of PR. Our findings suggest that the activation of specific EGF-induced intracellular pathways could decrease or modulate those induced by E2.