Methods for assessing proestrogenic and estrogenic activity of xenobiotics (environmental pollutants and therapeutic agents) are critically evaluated. The uterotropic assay in vivo and the binding affinity to the uterine estrogen receptor in vitro are still the preferred methods by most investigators. Because metabolism could markedly alter the activity of estrogens and proestrogens, in vitro methods that do not consider such possibilities have only limited utility. An in vitro method, which attempts to satisfy that requirement by combining metabolic capability with binding to the estrogen receptor, has become available. However, this method still needs considerable refinement and the assessment of its potential and limitations. In addition, there is a need for a facile method for determining whether a compound is a frank estrogen or a partial agonist/antiestrogen. These methods are considered in respect to their application for risk assessment. (Copyright (c) 1988 Pergamon Press plc.)