Although atrial natriuretic peptide (ANP) has been detected in the plasma of late gestation fetal sheep, stimuli that control its secretion and its function in regulating fluid volume are unclear. To determine stimuli that increase ANP secretion and to ascertain whether the response is a function of gestation we studied 20 chronically cannulated fetal sheep. The fetuses were divided into 3 groups; Group I (age range 118-129 days), Group II (age range 129-141 days) and Group III (age range 127-137 days) gestation. Arterial pressure was increased to within a physiologic range by infusing phenylephrine at 6 micrograms/min at 0.1 ml/min into the inferior vena cava of the fetus (Groups I and II). Corrected for body weight fetuses in Group I received 2 micrograms/kg/min whereas fetuses in Group II received 1.66 micrograms/kg/min. In the fetuses in Group III preload to the right side of the heart was increased by inflating an occluder cuff was placed around the ductus arteriosus. Systemic mean arterial pressure (MAP) increased significantly in fetuses in Groups I and II. Plasma ANP concentrations increased significantly in all fetuses. Plasma Renin Activity (PRA) decreased significantly in the fetuses in Group II. These results suggest that phenylephrine infusion and closure of the ductus arteriosus in utero increase circulating ANP in fetal sheep.