Epidemiological studies have indicated that females may be at greater risk of smoking associated lung cancer compared with males. Several lines of biochemical evidence support these observations. A possible role of circulating steroid hormones in the etiology of lung cancer has been hypothesized. In the present paper, we have studied the expression of the estrogen receptors (ER)-alpha and ER beta in histologically normal human lung tissue and lung tumor cell lines. Relative ER mRNA levels were measured by reverse transcriptase-PCR and normalized to the level of expression of the glyceraldehyde 3-phosphate dehydrogenase gene (GAPDH). In lung tissue, an ER alpha transcript was found at various levels in 38 out of 46 cases (83%). ER beta was expressed in all cases. The ERs were expressed at similar levels in females and males, and the levels of ER alpha and ER beta mRNA were significantly related (P<0.0001). Compared with the lung tissue, ER expression levels were lower in 16 human lung tumor cell lines and two immortalized human bronchial epithelial cell lines. Five of the tumor cell lines (31%) expressed detectable levels of ER alpha and both of the immortalized cell lines showed a weak ER alpha expression level. All cell lines expressed the ER beta. The lung cell lines BEAS-2B and DB354 showed significantly reduced cell proliferation in response to tamoxifen and a minor increased growth in response to 17 beta-estradiol. In conclusion, ER genes are abundantly expressed in both histologically normal human lung and lung tumor cell lines. This indicates a possible role of ERs in lung carcinogenesis.