We measured testicular human chorionic gonadotropin (hCG) receptors in 30 infertile men either before or 1, 3, 5, 7, or 14 days after a single administration of 5000 IU of hCG. For 5 days the administration of hCG significantly reduced the testicular binding of 125I-hCG compared with that of the testes before administration. From the 7th day the binding capacity began to increase and returned to the preadministration level 14 days after the treatment. Occupied hCG binding sites accounted for about half of the reduction in binding sites on the day after administration of hCG. After this time, however, the occupancy did not contribute so much to the reduction in binding sites. These findings suggest that the reduction in testicular hCG binding sites after a single administration of 5000 IU of hCG is due to not only occupancy but also down-regulation of the binding sites.