Estradiol-binding molecules have been found both in cytosol and nuclear extract of hepatocytes of the female green frog Rana esculenta. These molecules show the properties of an estradiol receptor (Re): high and specific affinity for estrogens (2.10-7.10 x 10(-10) M), stability of binding at 0 and 20 degrees, localization in the nucleus, and cytosolic versus nuclear binding shift in estradiol-treated frogs. In hepatocytes, both filled and unfilled Re is detectable in all stages of the R. esculenta annual cycle. It increases during the recovery phase (September to January) when vitellogenetic processes are active in the ovary. These changes are positively correlated with vitellogenin. Only nuclear filled Re, moreover, is positively correlated to level of circulating estradiol. This suggests a direct connection: plasma estradiol level versus nuclear filled Re versus plasma vitellogenin level.