In the adult, atrial natriuretic peptide (ANP) regulates renal and cardiovascular function when blood volume is expanded, when atrial pressure is increased, and when arterial oxygen content is decreased. In late gestation fetal sheep, plasma ANP concentrations are higher than in pregnant adults; however, ANP function in the fetus is unclear. To assess the possible role of ANP in mediating changes in pulmonary blood flow, we studied six chronically cannulated fetal sheep at 132-134 d gestation (term 145 d). We infused ANP in doses of 4.0 +/- 0.48, 16.0 +/- 1.9, and 64.0 +/- 7.7 ng/kg/min, and vehicle into all fetuses. ANP increased hematocrit, which suggests that blood volume decreased. Pulmonary blood flow, measured by the radionuclide-labeled microsphere technique, increased in response to the 4.0, 16.0, and 64.0 ng/kg/min dose ANP infusions from a control value of 126.5 +/- 32.2 to 141.8 +/- 26.9 to 170.4 +/- 37.2 to 300.8 +/- 84.8 mL/min/100 g (p less than 0.05), respectively, and calculated pulmonary vascular resistance decreased from a control value of 0.45 +/- 0.08 to 0.42 +/- 0.08 to 0.43 +/- 0.09 to 0.21 +/- 0.04 (p less than 0.05) mm Hg/mL/min/kg, respectively. Pulmonary blood flow decreased to 54.5 +/- 6.0 mL/min/100 g and calculated pulmonary vascular resistance increased to 0.81 +/- 0.09 mm Hg/mL/min/kg during the recovery period. Mean pulmonary and carotid arterial blood pressures, venous blood pressure, and heart rate did not change significantly. Thus, ANP may play a role in maintaining right ventricular output in the fetus by increasing pulmonary blood flow through its ability to decrease pulmonary vascular resistance.