Immunohistochemical investigations of estrogen receptors in normal and neoplastic squamous epithelium of the vulva. Atrophic disease of the vulvar epithelium can be treated with steroids, but carcinoma of the vulva cannot be influenced with any hormone therapy. Seventy-one vulvar specimens were tested for estrogen receptor (ER) content by means of immunohistochemistry. Slight ER staining was found in nonkeratinizing squamous epithelium in 17 of 22 cases. A weak ER reaction in the basal and parabasal layers was found in only 2 of 17 specimens of keratinizing squamous epithelium. However, no ER was found in any neoplastic tissue of the vulva or the adjacent stroma. The loss of ER in neoplastic cells could explain the clinical experience that antihormonal treatment of vulvar carcinomas produces no appreciable improvement. 