This study was designed to investigate whether the combination of castration with estrogen treatment for 6 weeks (combined treatment) further inhibits growth of the Dunning R3327 rat prostatic adenocarcinoma as compared with castration alone. Combined treatment arrested tumor growth more effectively than castration. Combined treatment also induced morphological changes in both tumor stroma and epithelium that were not found in tumors from castrated animals. The volume density of the tumor epithelium was reduced and the volume density of the tumor stroma was increased by the combined treatment as compared with castration alone. The number of tumor epithelial cells was calculated by morphological methods: combined treatment lowered the number as compared with castration alone. The number of tumor epithelial cells was similar in castrated and intact rats. Both combined treatment and castration alone reduced tumor epithelium cell size as compared with tumors from intact rats. These findings suggest that estrogen may have direct effects on total number and function of prostatic tumor cells.