To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity. To enhance the rectal absorption of hCG, the effectiveness of its coadministration with α-cyclodextrin (α-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and α-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of α-CyD. The AUC_0→48 observed after coadministration of hCG and α-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and α-CyD at 10 mg/kg body weight. HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2±3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration. On the other hand, the maximum level of testosterone concentration (40.0±12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with α-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0±11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4±0.9 ng/ml) observed before the administration. These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.