The effects of orchidectomy, combined oral/parenteral estrogen, and single-drug parenteral estrogen therapy on the serum levels of testosterone (T), 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA) and its sulfate (DHAS), sex-hormone-binding globulin (SHBG), and albumin were studied in 48 patients with prostatic cancer. Both estrogen treatment regimens were as effective as orchidectomy in reducing circulating levels of T and A-4. Orchidectomy caused a slight decrease in DHAS levels. Oral estrogens profoundly decreased the serum levels of DHAS and, to a lesser extent, levels of DHA and of albumin, while parenteral estrogens had no effect in this respect. SHBG serum levels were highly increased by oral estrogens, slightly increased by parenteral estrogens, and unaffected by orchidectomy. The more pronounced effects of oral estrogens on circulating adrenal androgens may reflect an altered liver metabolism associated with this route of administration.