The direct inhibitory effects of estrogens on human testicular functions were investigated with a testicular organ culture technique. 125I-labeled human chorionic gonadotropin (125I-hCG) bindings in testes cultured in media containing diethylstilbestrol diphosphate (DESDP) began to dose-relatedly decrease a day after the start of the culture, and this decrease remained relatively constant during the 5-day culture. On the other hand, testosterone produced by the cultured testes time-relatedly decreased during the 5-day culture. From the above results it may be concluded that the direct inhibitory effect of estrogens on human testicular androgen production consists of not only the loss of testicular hCG receptors but also of other mechanisms at a distal step from hCG receptor activation.