The estrogen receptor model has revised to make it compatible with new data on subcellular localization of the receptor and physical characteristics of solubilized versus immobilized receptors. Our current model suggests that receptors, with or without bound estrogen, are present in the nuclear fraction. Furthermore, the receptor behaves as if it were immobilized or bound to some nuclear constituent at all times. Thus, the association of the estrogen-free receptor (unbound receptor) to a target site in the nucleus is considered to be the critical event in defining the nature of the response to estrogenic hormones.