Although castration levels of serum androgens are consistently achieved after 2-3 weeks of treatment with luteinizing hormone-releasing hormone (LHRH) agonists, the administration of these peptides alone in adult men is always accompanied by a transient increase in plasma testosterone and dihydrotestosterone levels, which lasts for 5-15 days at the beginning of treatment and is accompanied by disease flare-up in some cases, thus seriously limiting the acceptability of this otherwise efficient and well-tolerated treatment. The present data show that the simultaneous administration of a pure antiandrogen neutralizes the influence of the transient increase in serum androgens on prostate cancer, as indicated by the 60% decrease in serum prostatic acid phosphatase observed within 5 days of combined treatment with an LHRH agonist and a pure antiandrogen. The addition of a pure antiandrogen thus makes fully acceptable the use of LHRH agonists as an advantageous substitute for surgical castration and estrogens in the treatment of prostate cancer.Cancer of the prostate is the second cause of death due to cancer in men, with an estimated minimum of 60,000 newly diagnosed cases annually in the United States. After the pioneering studies of Huggins and Hodges (1), most of the efforts during the last 40 years have been aimed at eliminating the influence of testicular androgens on the growth of the cancer by surgical castration or by treatment with estrogens, which causes a decrease in circulating androgens. Such treatments provide a temporary objective and/or subjective improvement in 60%-70% of cases of advanced prostate cancer (2, 3). However, surgical castration is not always well accepted by patients, and treatment with estrogens causes serious cardiovascular complications, which often offset the benefits (4). There was thus the need for a more acceptable, well-tolerated, and possibly more efficient form of hormonal therapy.The observation that treatment of experimental animals with luteinizing hormone-relasing hormone (LHRH) agonists causes a marked inhibition of testosterone secretion, accompanied by a decrease in prostate weight (5), offered the possibility of a new approach in the treatment of prostate cancer. Fortunately, among the species studied, man is the most sensitive to the inhibitory action of LHRH agonists on testicular androgen formation, and thus medical castration can be easily achieved (5-10). Although the chronic administration of these peptides in adult men completely blocks testicular androgen formation with no secondary effects other than those related to hypoandrogenicity, a serious limitation pertains to the transient increase in serum androgen levels, which lasts for 5-15 days at the beginning of treatment. This increase in serum androgens is accompanied by disease flare-up in a significant proportion of cases (9), thus seriously limiting the use of LHRH agonists alone in treating prostate cancer, at least during the first 2 weeks of treatment.The present study shows that the simultaneous...