PIP: Most antiandrogens appear to act by binding to the androgen receptor and competitively inhibiting the binding of testosterone and cihydrotestosterone to the receptor. Focusing on those compounds which appear to inhibit androgen receptor mediated responses, this review discusses the chemistry of those antiandrogens which have been studied to the extent that their mechanism of action is at least partially understood, outlines the mechanism of androgen action as it is currently understood and suggests how antiandrogens might fit in with this mechanism, indicates the major metabolites of several important antiandrogens, and discusses the clinical applications of several antiandrogens. Cyproterone acetate has been studied extensively as a potential male contraceptive. Although it was recognized that 100 mg of cyproterone acetate per day inhibited spermatogenesis, that dose also reduced libido and potency. Following the administration of 10 or 20 mg of cyproterone acetate per day to 15 males for 26 weeks, the following observations were made: the number of motile sperm was reduced; the quality of their motion was impaired; and the ability of the sperm to penetrate cervical mucus was decreased. Sperm density was also suppressed, but neither it nor sperm motility were inhibited to the extent necessary for contraception. Antiandrogens have been demonstrated to be beneficial in treating 5 clinical syndromes or diseases: acne, seborrhea, hirsutism with or without menstrual abnormalities; precocious puberty; benign prostatic hypertrophy; cancer of the prostate; and sexual deviates. Since 3 of these conditions are very common, effective and safe treatment would have a large market. At this time, antiandrogens are widely used in Europe for treatment of seborrhea, acne, and hirsutism and a large Veterans Administration Cooperative Study in the US was approved but has not yet been funded to compare antiandrogens with other treatments for cancer of the prostate. Studies to assess antiandrogen interaction with other hormones or drugs have been limited. Side effects in the female have been best evaluated when cyproterone acetate was administered in combination with ethinyl estradiol. In 46 women followed over 317 cycles, side effects were similar to those reported with estrogen-progestin contraceptives. Administration of 10-20 mg of cyrproterone acetate per day to males caused no significant side effects, but 100 mg or more/day has caused loss of libido, impotence, gynecomastia, tiredness, weakness, decreased efficiency, weight gain, drying and desquamation of skin over the legs, and loss of hair on the trunk and pubic area.