Fetal lambs treated with sheep anti-mouse nerve growth factor antibodies (anti-NGF) at 80 days gestation subsequently showed a diminished cardiovascular response to intravenous infusion of tyramine (1 mg/min over 10 min) and no significant change in plasma norepinephrine concentrations as measured by reversed-phase high-pressure liquid chromatography and electrochemical detection. At autopsy at 135 days gestation, catecholamine content of the heart, thyroid, kidney, and ileum was reduced by greater than 70% compared with age-matched control fetuses. The anti-NGF-treated fetuses were thus judged to have impaired sympathetic function. When made hypoxemic (arterial PO2 12-14 Torr) for 1 h at 120 or 130 days gestation, anti-NGF-treated fetuses showed no significant change of arterial pressure, heart rate, or plasma catecholamines, whereas control fetuses showed bradycardia, a 28% increase in arterial pressure, and a 670% increase of plasma norepinephrine concentrations. These results suggest that the increase of arterial pressure that occurs during hypoxemia in fetal lambs between 120 and 135 days gestation is attributable to increased activity of the peripheral sympathetic nervous system. The adrenal medulla appears to contribute to the plasma catecholamine pool at rest, but the lack of increased plasma catecholamines during hypoxia after anti-NGF implies that the adrenal medulla was unable to release catecholamines. Possible reasons for this are discussed.