The lungs play an important role in the metabolism of vasoactive substances including endogenous amines. The role of pulmonary clearance of circulating norepinephrine has not been well defined in the young lamb (7–8 d of age). Using radiolabeled tracer norepinephrine in acutely instrumented lambs, we determined thein vivopulmonary clearance and spillover rate of norepinephrine under baseline and hypoxic conditions. The fractional extraction of norepinephrine, the percent removed on a single pass through the pulmonary circulation, was 23 ≤ 2%. The corresponding pulmonary clearance rate was 61 ≤ 10 mL/kg/min and the net pulmonary norepinephrine removal rate was 0.41 ≤ 0.14 nmol/kg/min. This clearance represented over 70% of whole body norepinephrine clearance. The spillover of synaptic norepinephrine was 0.22 ≤ 0.13 nmol/kg/rain. During hypoxia, animals showed significant increases in pulmonary artery pressure and resistance. Fractional extraction of norepinephrine decreased to 16 ≤ 3%, p < 0.005. Pulmonary clearance decreased to 31 ≤ 7 mL/kg/min, and net pulmonary norepinephrine removal rate decreased to 0.27 ≤ 0.07 nmol/kg/min. These results demonstrate that pulmonary clearance plays a significant role in norepinephrine clearance in 1-wk-old lambs. Alteration of norepinephrine clearance during physiologic states such as hypoxia may be important in the pathophysiology of altered pulmonary vascular resistance in newborn animals.