Suppression of plasma testosterone levels from a mean of 760 ng/dl to a mean of 295 ng/dl could be induced in normal young adult men 24 h after a single injection of 2 mg aqueous 17 beta-estradiol. Maximum suppression to 123 ng/dl was noted 36 h after estradiol administration. Neither LH nor FSH levels were similarly affected. After administration of 5000 IU hCG to a similar group of subjects, daily blood samples were obtained for testosterone and estrogen. Maximum testosterone levels of 2060 ng/dl (basal, 784 ng/dl) were seen 96 h after hCG administration. Maximum estrogen levels of 13 pg/ml (basal 73 pg/ml) were seen 36 h after hCG administration. The testosterone response to hCG could be attenuated by preceding hCG administration with an injection of 17 beta-estradiol. These results can be explained by the concept of enzyme inhibition; estrogen acts directly on the Leydig cell to effect changes in the activities of certain enzymes important for testosterone synthesis. Whether endogenous estrogen production by the Leydig cell may be important in this postulated short loop feedback is as yet unclear.