Studies of hormonal transfer have shown that the human placenta permits negligible passage of several labeled polypeptide hormones. In order to determine whether it also prevents maternofetal transfer of glucagon, nine pregnant women of 15–17 weeks gestation were evaluated during legal therapeutic abortions by abdominal hysterotomy. The plasma concentration of 125I-glucagon was maintained by continuous iv infusion of the labeled hormone at the following rates: 20 μCi/hr for 3–4 hr in four women; and 60 μCi/hr for 1–1.5 hr in the other five. In an additional pregnant woman who received no hormonal infusion, the fractional disposal of 125I-glucagon by the fetus in situ was evaluated after direct rapid injection of the radioiodinated hormone into the fetal carotid artery. The plasma concentrations of the labeled glucagon were measured by specific immunoprecipitation. Even with maternal plasma concentrations of radioactive glucagon between 599 and 1289 cpm/ml during maternal infusions, no 125I-glucagon was detected either in the umbilical venous or arterial plasma, or in the amniotic fluid. In the fetus, the fractional disposal of 125I-glucagon was 0.085 min−1. Thus, the fractional rate at which maternofetal 125I-glucagon transfer enriches the fetal plasma glucagon pool apparently is negligible compared to the fractional disposal rate. Early in gestation, therefore, the human placenta is an effective barrier to the rapid maternofetal transfer of 125I-glucagon, and equilibration of maternal and fetal plasma glucagon levels by diffusion does not occur.