Estrogen receptor (ER) was demonstrated in nontumorous and adenomatous human pituitaries by autoradiography and biochemical assays. In the present study, we investigated ER mRNA by in situ hybridization applied on paraffin section of 9 nontumorous pituitaries obtained at surgery or autopsy and 109 surgically removed adenomas. In nontumorous pituitaries, in situ hybridization combined with immunocytochemistry revealed hybridization signal in GH-, PRL-, ACTH-, TSH-, and LH/FSH-immunoreactive cells, with the highest intensity in PRL-immunoreactive cells. ER mRNA was also localized in Crooke's cells, corticotrophs extending to posterior lobe, cells lining the pars intermedia cavities, and squamous nests of pars tuberalis. The neurohypophysis, endothelium, and connective tissue expressed no ER gene. ER mRNA was present in all adenoma types, including somatotroph, lactotroph, mixed somatotroph-lactotroph, mammosomatotroph, acidophil stem cell, functioning and silent corticotroph, thyrotroph, gonadotroph, null cell adenomas, and oncocytomas. The strongest signal was seen in some lactotroph and mammosomatotroph adenomas. In 9 lactotroph adenomas exposed to bromocriptine (long-acting repeatable injectable form), the hybridization signal was weak or absent, suggesting that suppression of ER gene plays a role in the inhibition of PRL synthesis and tumor growth.