An LHRH agonist was first administered to a prostate cancer patient 16 years ago in 1980 while combination therapy with an LHRH agonist and a pure antiandrogen was first administered 14 years ago in 1982. We take this opportunity to review briefly the events which, in our opinion, led to such fundamental changes in the endocrine therapy of prostate cancer. Following the observations of Huggins and his colleagues in 1941, orchiectomy and treatment with high doses of estrogens remained the standard therapy of prostate cancer for 50 years. Discovery of the structure of LHRH in 1971 by Schally and his colleagues stimulated the synthesis of highly potent analogs of LHRH with the objective of treating infertility. However, difficulties were met in finding the proper schedule of administration as well as the dose of LHRH agonists which could maintain stimulatory effects upon repeated administration. In fact, contrary to the expectations of a stimulatory effect, we found in 1977 that treatment of adult male rats with an LHRH agonist for a few days caused some inhibition of ventral prostate and seminal vesicle weight, although the inhibitory effects achieved were small compared with those of castration. It was then believed that the high serum LH levels induced by LHRH agonist treatment caused desensitization of the steroidogenic response in the testes.