PURPOSE Many epidemiologic studies indicate an increased incidence of certain vision threatening conditions in postmenopausal women. These data suggest that changes in sex steroid homeostasis may affect the physiology of the eye. To provide support to this hypothesis, the expression of estrogen receptor alpha (ERalpha) in human eye tissues was investigated. METHODS Complementary studies including RNA analysis by reverse transcription polymerase chain reaction, western blot analysis, and immunocytochemistry were used to provide evidence of ERalpha expression. Protein detection was carried out using a mouse monoclonal antibody raised against an epitope located in the ligand binding domain of the human receptor. Cellular localization was studied on formalin-fixed paraffin-embedded eye sections using conventional immunohistochemical techniques. RESULTS Gender and age differences in ERalpha mRNA expression were observed in retina. The 65-kDa ERalpha protein was detected in the retina and retinal pigment epithelium (RPE) of young female eyes but not in eye tissues dissected from men and postmenopausal women. Immunocytochemistry corroborated ERalpha staining of a young female neurosensory retina and RPE. In addition, ERalpha could be detected in the ciliary body, in the iris, and in the epithelium of the lens. CONCLUSIONS The presence of the ERalpha in the human eye suggests that the sex steroid hormone axis may play a role in the pathogenesis of certain ocular diseases.