Whole MCF-7 human breast-cancer cells were irradiated at −78°C in a calibrated Gammacel 6OCo irradiator. Freezing or storing conditions induce neither an alteration of the viability of cells nor a change in estradiol binding activity. Hexosaminidase was used as internal marker, and we measured the radiation inactivation size (RIS) of the estrogen receptor in whole cells. After various cell treatments, the estradiol binding unit always presents a molecular mass of 25 kDa. This value, which corresponds to the size of the defined hormone binding domain of the estrogen receptor, suggests that the energy delivered to the protein by the radiation is efficient to inactivate estradiol binding only when the hit occurs directly in the smaller hormone binding domein.