The existence of an estrogen receptor (ER) on the plasma membrane has been supported by data emerging from numerous laboratories over the past 20 years. However, this receptor has not yet been isolated. Original reports of a cell membrane protein that could bind and rapidly respond to 17beta-estradiol (E2) were supported by evidence that a putative membrane receptor could effect a variety of signal transduction events. Recent studies have shown that the nongenomic actions of E2 can be mediated through the plasma membrane ER.