PIP: An in vitro study of the nuclear uptake of estradiol 17 beta (E2) in mammary tumor tissue utilized 16 specimens taken at mastectomy. Dextran/charcoal assay of cytosol receptor was used in this tissue slice technique, based on uptake of tritiated E2. 9 tumors had receptor concentrations from 7.3-496 fmol/mg of cytosol protein. No nuclear uptake was detected in 4 of these tumors, in spite of the fact that 1 of these had the highest concentration of cytosol receptor measured. The remaining 7 tumors contained no cytosol receptor and showed no detectable nuclear uptake of E2. 3 cases yielded protein-bound radioactivity in the column eluate (Sephadex) sufficient to allow sucrose gradient analysis. The major radioactive peak of 1 of these moved slightly faster than bovine serum albumin, i.e., in the 5S region charactersitic of the nuclear receptor found in other estrogen-sensitive tissues. It is conclded that hormone independency in mammary tumors containing E2 cytosol receptor may be caused by failure of translocation or binding of E2-receptor complex to the cell nucleus.