The contribution of different parts of natural and synthetic steroid molecules in their binding to high affinity estradiol receptor preparations obtained from whole human uteri was assessed. Of 55 compounds used in the study, 38 contained the steroid nucleus. The affinity (in terms of association constants) of the compounds for the receptor was determined from competitive studies with radioactive estradiol. Consequently, the compounds could be grouped according to their association constants for the receptor. The contribution of the individual functional groups of the steroid molecule to the binding process was analyzed. The preliminary quantitative evaluation of the contribution was derived from the equation: log K = log.DELTA.Ks + .SIGMA. log.DELTA.KF where Ks is the contribution of the basic 1,3,5-(10)-estratriene skeleton, KF the associated functional groups and K the affinity constant for the entire molecule. The main positive contribution in the binding was provided by skeleton and the 3-hydroxyl group. Functional groups present at the 3 or 17 position act independently of each other in the binding process. The possible synergism between the functional groups and the steroid skeleton was discussed.