Our perspective is that the mechanisms separating the action of estrogen agonists and antagonists involve contrasting transitions in receptor conformation which determine receptor access to different chromatin regions. Although we have suggested that size related exclusion of receptor may provide one manner for determining chromatin access (Pavlik et al., 1985), additional mechanisms may also be involved. The most recent evidence from several laboratories supports this perspective and indicates that estrogen receptors associated with antiestrogens are competent with respect to activation and response elicitation. Thus, we believe that an important course for future effort will be to define chromatin interactions that are limited to estrogen receptors complexed with either agonist or antagonist.