The distribution of <sup>125</sup>I-labeled HCG and asialo-HCG after intravenous injection was studied quantitatively and by radioautography in the luteal, liver and kidney tissue of the mouse. It was found that the disappearance rate of HCG from the blood was markedly enhanced after desialylation. Simultaneously the uptake of radioactivity in the liver was increased and that in the luteal tissue was decreased. In radioautography <sup>125</sup>I-HCG was localized exclusively over the Kupffer cells, whereas <sup>125</sup>I-asialo-HCG showed labeling of the parenchymal cells. This difference in the cellular site for HCG and asialo-HCG indicates that two mechanisms are active in the liver for the glycoprotein inactivation. Minor differences in the molecular structure may influence the mechanism and site of the hormonal uptake. The kidneys were relatively less important in the uptake of HCG and asialo-HCG, but they appeared to be more involved in the disposal of LH and FSH from the blood.