Effects of estrogen and tamoxifen on the synthesis of secretory proteins were examined using estrogen-responsive mouse Leydig tumor. Estrogenization of host mice bearing the tumor (T 124958-R) resulted in the appearance of the secretory glycoprotein with a molecular weight of 34,000 which was detected by incubation of dispersed cells or minced tissues with [35S]methionine. The discontinuation of in vivo estrogenization decreased the growth rate of the tumor with the simultaneous disappearance of this secretory protein. Transplantation of tumor grown in non-estrogenized mice showed reacquisition of estrogen dependency in terms of tumor growth as well as secretory glycoprotein synthesis. Furthermore, tamoxifen administration to mice enhanced the tumor growth with simultaneous induction of this secretory protein. These results suggest that this secretory glycoprotein can be used as a marker for estrogen- or tamoxifen-dependent growth in vivo.