Research on Selective Estrogen Receptor Modulators (SERMs) has been driven by interest in discovering target selective molecules. In view of such significance, the present work explored the pharmacophores of estrogen receptor (ER) subtypes specific binding affinities of diverse compounds belonging to the category of bridged bicyclic-1,1-diarylethylene derivatives. Implementing classical QSAR and CATALYST based space-modeling approaches, it has been explored that attachment of aryl ring systems to unsaturated linkages, availability of phenolic hydroxyl group, global hydrophobicity, and stereochemistry of certain functional groups might be important for governing the subtype specific estrogenic behavior of this group of compounds. Supplementing this deduction, critical interfeature distances between hydrogen bond acceptor, hydrophobic, and ring aromatic features along with steric influence are found to primarily influence the ER-subtypes specific binding of this series of compounds. © 2007 American Chemical Society.