Histrelin, a potent luteinizing hormone releasing hormone (LHRH) agonist, and flutamide, an antiandrogen, were administered to intact and adrenalectomized rats to determine the role of adrenal androgens in the additive effects of the two drugs on prostate regression. Each compound, given separately, was effective in decreasing prostate weights in intact rats. When given together, additive effects were demonstrated by even greater atrophy of the prostates. It has previously been proposed that this additive effect may be primarily attributed to the ability of the antiandrogen to block the action of adrenal androgens. However, in adrenalectomized rats, the combination of histrelin and flutamide still produced a greater reduction in prostate weights than did either drug alone, indicating that the role of adrenal androgens in this effect is negligible. This experiment also was repeated with castrate, androgen-supplemented rats, and the additive effects previously described were not observed. In a final experiment, prostatic atrophy in castrate rats was not enhanced by either adrenalectomy or flutamide treatment. Thus, the additive effects of histrelin and flutamide appear to focus on testicular rather than adrenal androgens.