Two different estrogen receptors (ER-and ER-) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ERwas considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-in the three types of prostatic specimens studied. Epithelial immunostaining for ER-was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-in the epithelium and ER-in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ERand ER-in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.