There are conflicting reports in the literature regarding the response of the rat prostate to various androgen/estrogen combinations. The reason for these conflicting results has been unclear. The purpose of the present study was to assess factors that may determine the effect of sex hormones on rat prostate growth. The results of this study demonstrate that the prostates of Lewis rats respond differently to sex hormone combinations than do those of Sprague Dawley rats. Young rats have a different prostate hormone responsiveness than do old rats. The presence or absence of the testes alters the responsiveness of the prostate gland to androgen-estrogen combinations. These results suggest that strain, age, and the presence of the testes are important factors which will influence the response of the rat prostate to hormonal manipulation. The importance of these factors should be considered in the design of experiments which deal with the response of the rat prostate to hormone manipulation.