Because the liver is an estrogen-sensitive organ and such sensitivity necessitates the presence of an hepatic estrogen receptor, we assayed whole human liver cytosol for the presence of estrogen receptor. Scatchard plot analysis of specific [3H]diethylstilbestrol binding to whole human liver cytosol from both sexes demonstrated hormone binding that is of high affinity (Kd = 10(-10)M) and low capacity (1-10 fmol/mg cytosol protein), and that is saturable and specific for steroidal and nonsteroidal estrogens, but not for other steroids. The protein can be further characterized as an estrogen receptor by its binding to heparin-Sepharose. In addition, gel filtration chromatography of [3H]estrogen-labeled cytosol on Sephadex G-100 indicates that potentially contaminating proteins, such as albumin and sex-steroid-binding globulin, do not bind [3H]estrogen in whole cytosol. We conclude that human liver from both sexes has estrogen receptor and that the presence of estrogen receptor in human liver explains the sensitivity of the human liver to estrogen.