The importance of sialic acid residues for combination of hCG with ovarian receptor sites was evaluated by comparing the capacities of intact and desialylated hCG to compete with 125I—labeled hCG for binding to ovarian tissue in vivo and in vitro. Direct uptake of 125I—labeled asialohCG was also examined in vitro. For competitive binding studies, intact hCG was labeled with 125I and shown to be indistinguishable from the unlabeled hormone by gel nitration, gel electrophoresis, electrofocusing and biological assay. Intravenous administration of 200 ng 125I—hCG to immature female rats was followed by maximum ovarian uptake of 6–12% of the injected radioactivity at 2 hr, with progressive reduction of tracer binding when 100–1200 ng hCG was added to the labeled hormone before injection. The ability of asialohCG to compete with 125I—hCG for ovarian uptake in vivo was reduced to 3% of the activity of the intact hormone, consistent with the rapid clearance and consequent low biological activity of the desialylated derivative in vivo. By contrast, the inhibition by asialo—hCG of 125I—hCG binding to ovarian homogenate in vitro was slightly increased, rather than reduced, by desialylation. The direct uptake of 125I—hCG by ovarian homogenate in vitro was also slightly greater than that of the labeled intact hormone. These results have confirmed that the sialic acid residues of hCG play no significant role in specific hormone uptake by gonadal tissue, as desialylated hCG shows normal or enhanced affinity for ovarian binding sites in vitro. (Endocrinology91: 463, 1972)