The higher frequency of human lung adenocarcinoma in females than in males, strongly suggests the involvement of gender dependent factors in the etiology of this disease. This is the first investigation of estrogen receptor (ER) beta in human lung. Immunohistochemical staining revealed ERP expression in normal lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous lesion for adenocarcinomas, Adenocarcinomas showed significantly higher expression of ERP than squamous cell carcinomas. On the contrary, ER alpha expression was not detected in all cases. The functional integrity of ERP such as the binding ability to estrogen responsive element (ERE) and transcriptional activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony formation of this cell was significantly reduced in the presence of pure antiestrogen. We conclude that ERP, but not ER alpha, is present in lung tissues with an important physiological function in normal lung. Furthermore, ERP may play a role in growth and development of adenocarcinomas,