Flutamide is rapidly metabolized by hydroxylation of the side chain to SCH 16423 (alpha, alpha, alpha-trifluoro-2-methyl-4'-nitro-m-lactotoluidide), the major metabolic product in all species studied, which is biologically active in vivo and in vitro studies. Flutamide exhibits its antiandrogenic activity by inhibiting androgen uptake and/or inhibition of nuclear binding of the androgens in the target tissues. At daily doses from 1 to 50 mg/kg body weight, flutamide reduced seminal vesicle and ventral prostate weights of intact male rats without affecting sexual potency. In addition, flutamide reduced the rate of DNA synthesis in the prostate of rats to a greater degree than other steroidal antiandrogens. The antiandrogenic activity was corroborated by the inhibition of androgen-induced prostate hypertrophy in orchiectomized rats through the use of testosterone, testosterone propionate, dihydrotestosterone, androstenedione, and dehydroepiandrosterone. Flutamide, given orally, reduced prostatic size in aged dogs with benign prostate hyperplasia after six weeks and one year. The baboon prostate was also reduced in size when flutamide was administered three times a week for four weeks.