We measured pulmonary vasodilation induced by histamine, H1 and H2 antagonists, and H1 and H2 agonists in chronically prepared, normally oxygenated fetal sheep in order to study the response of H1 and H2 stimulation in late gestation. Blood flow was measured in the left pulmonary artery; pressures were measured in the main pulmonary artery and abdominal aorta. Histamine administered into the left pulmonary artery caused dose-dependent increases in left pulmonary blood flow without changes in either pulmonary arterial or aortic pressures. Cimetidine (H2 antagonist) and/or diphenhydramine (H1 antagonist) shifted the histamine dose-response curve to the right. 2-Pyridylethylamine (H1 agonist) and dimeprit (H2 agonist) caused vasodilation which was selectively blocked by its respective antagonist. We conclude that both H1 and H2 stimulation cause pulmonary vasodilation in the ovine fetus.