Mouse 3T3 fibroblasts (clone A31) were stably transfected with human estrogen receptor (hER). Among the four sublines expressing functional hER at approximately 10(4) estrogen binding sites/cell, three retained a non-transformed morphology and growth characteristics while the fourth displayed a transformed phenotype (criss-cross growth, lack of density arrest, reduced dependence on exogenous growth factors). Estradiol (E2) had no effect on the growth of the three non-transformed hER expressing sublines. In contrast, low concentrations (1 to 20 nM) of E2 strongly inhibited the proliferation of the subline with transformed phenotype and high (100 nM) concentrations were toxic in these cells.