AbstractA QSAR is obtained for affinity towards the gestagenic receptor for a series of 55 progesterone derivatives (r = 0.935), using the MTD‐method, with MTD for steric misfit and f a corrected relative hydrophobicity. Acceptable stability of regression coefficients of vertex attributions are obtained when this QSAR is compared with previous QSAR's for a reduced series of progesterone derivatives and for testosterone derivatives. Acceptable predicted activities for test molecules (r2= 0.71) and acceptable results in a cross validation‐like procedure (r2= 0.76) were obtained. These are strong arguments that our MTD results correspond to some real features of the gestagenic receptor site. In order to explain relative success of the MTD‐method in QSAR's for steroids, as compared to other methods, molecular aspects of the receptor‐effector interaction are discussed in relation to QSAR‐methodology. Recent computational chemistry approaches are based upon drug molecule‐receptor site energy calculations, assuming a fixed conformation for the receptor site. If the drug molecules are “hard” (rigid), the steric misfit with a “soft” (conformationally flexible) receptor site may be avoided by induction of different local conformational ch