Estrogens induce rapid (non-genomic) and delayed (genomic) effects on the target cells. The early effects include induction of signal transduction pathway within seconds, whereas the delayed responses require hours and involve transcription and translation. The rapid effects of estradiol (E) on the vaginal epithelial cells (VEC) involved calcium uptake within seconds via the induction of phosphoinositol lipid metabolism as reported in our earlier studies. In this study, we demonstrate the presence of classical estrogen receptors (ER) on the plasma membrane of VEC of the rats. Immunoreactive bands of 67, 56 and 35 kDa are detectable in the membrane fractions (mf) using antibodies recognizing different epitopes of ER alpha. We have also been able to purify a protein having a mass of 67 kDa from the detergent-soluble fraction of the plasma membrane of VEC, which shows properties identical to the classical receptor purified from the cytosolic fraction of the cells. The membrane receptors get dissociated upon binding to the ligand. Besides a role in signal transduction events induced by estradiol, the membrane estrogen receptors may have an important role to play in translocation of the steroid to the cytosolic compartment.