Infusion of gastrin, G-171, at 0.4 μg/min into either the maternal or fetal venous circulation of six late gestation sheep was associated with increases in serum gastrin concentration in the infused circulation and reciprocal decreases in the serum gastrin concentration in the other circulation (contraplacental) that perfused the placenta. Pentagastrin infusion at 0.4 μg/min was associated with an increase in C-terminal specific gastrin immunoreactivity in both the infused and the contraplacental circulations. These observations suggest that biologically active fragments of gastrin, but not the intact molecule, may cross the ovine placenta. An alternative explanation for our results is that gastrin infusion into either the maternal or fetal circulation which perfuses the placenta may result in the release of an inhibitor (ie., somatostatin) into the other circulation. Of broad importance, these observations indicate that although intact polypeptide hormones may not traverse the placenta, their concentrations in maternal and fetal sera may not be as independent as previously believed. Serum gastrin half-life values in late gestation sheep fetuses, lambs, and ewes were determined to be 13.7 ± 1.9, 16.7 ± 2.6, and 15.2 ± 2.8 min, respectively. These similar values indicate that the relatively high serum gastrin concentrations observed in near-term sheep fetuses are not the result of pro-longed half-life in the fetus.