Androgen antagonists offer a potentially useful treatment for androgen mediated diseases such as: prostate cancer, benign prostatic hyperplasia, seborrhea, androgenic alopecia and precocious puberty. A recent report from the world health organization revealed that carcinoma of the prostate is the second most commonly diagnosed cancer after skin cancer in the male population in U.S.A. and the second most common cause of death after that of lung. Since testosterone is reduced by NADPH in the presence of the enzyme 5-alpha-reductase into the more active 5-alpha-dihydrotestosterone which interacts more effectively with the androgen receptors, this fact indicates very clearly that the logical site of the therapeutic intervention should be this last step. In this paper we describe the synthesis and pharmacological evaluation of new 3-beta-substituted-4,16-pregnadiene-6,20-dione derivatives. These compounds were prepared from the commercially available 16-dehydropregnenolone acetate. These steroidal derivatives were evaluated as antiandrogens as well as 5-alpha-reductase inhibitors. The results from the in vitro studies with 5-alpha-reductase enzyme from hamster and human prostate showed that these compounds exhibited much higher 5a-reductase inhibitory activity than the presently used Proscar, (finasteride) the drug of choice for the treatment of androgen dependent prostatic afflictions. A mechanism for the inhibition of the enzyme 5-alpha-reductase by these progesterone analogues is also proposed.