The effects of luteinizing hormone‐releasing hormone (LHRH) agonist (Zoladex) treatment on hormone‐dependent rat prostate adenocarcinoma (R3327‐H) were investigated based on changes in tumor volume and histology. Tumor‐bearing rats were treated for 10 weeks with Zoladex in depot preparation by implantation every 2, 4, or 6 weeks. Tumor growth rate was similar in the castrated group and in the rats treated every 2 weeks with Zoladex. This growth rate was significantly slower than in animals treated with Zoladex every 6 weeks and the nontreated group. The growth rate in rats treated every 4 weeks appeared to be faster than that in the castrated animals (not significant). Changes in testosterone levels measured during Zoladex treatment correlated with tumor growth kinetics. Zoladex implantation yields effective and complete androgen deprivation only in the rats with two weekly depot renewal regimen. Tumor histology indicated that the stromal as well as the glandular epithelial cells responded to both castration and to Zoladex treatment. However, in tumors from rats treated with Zoladex every 4 and 6 weeks progressive increasing signs of restoration of normal elements, comparable to non‐treated tumors were observed. These results strongly suggest that careful attention has to be paid to the timing of LHRH depot renewal in prostate cancer treatment.