Simple alkyl phenols have been tested for their ability to prevent the binding of [3H]estradiol and to displace the prebound hormone from estrogen receptors of [rat] uterine cytosols. Tetrahydronaphthol, an analog of the A and B rings of estradiol, is highly effective in preventing the forward binding of estradiol. p-sec-Amyl phenol (pSAP) with a flexible alkyl chain corresponding to the B ring of estradiol is highly effective at 0.degree. C in displacing estradiol which was prebound by the receptor. Both compounds were more effective at 0.degree. C than at 23.degree. C. The data are discussed in terms of sequential conformational changes which might be required for the binding and release of the natural hormones and their possible relevance to receptor action.