The present invention provides isolated nucleic acids encoding full-length human estrogen receptor-.beta. (hER.beta.), which comprises 530 amino acids. The invention also provides isolated hER.beta. polypeptides and hER.beta.-reactive antibodies, including those that specifically recognize amino acids 1-45 of hER.beta.. The invention also encompasses methods for identifying hER.beta.-interactive compounds, including agonists, antagonists, and co-activators.