SummaryWe compared the concentration-response relationship of intralobar pulmonary arteries tol-norepinephrine with that of femoral arteries from newborn lambs. In addition, the effect of inhibition of the neuronal and extra-neuronal uptake mechanisms on these concentration-response relationships was examined. Concentration-response curves on 10 intralobar pulmonary arteries were performed with and without inhibition of the uptake mechanisms. Uptake inhibition shifts the curve to the left; thus, the -log EC50with uptake inhibition (6.63 ± 0.15) is greater than that without uptake inhibition (6.13 ± 0.14). Similar curves on 10 femoral arteries demonstrated that the -log EC50with and without uptake inhibition (6.20 ± 0.13 and 6.00 ± 0.04, respectively) are not statistically different.Because, in the presence of intact uptake mechanisms the concentration ofl-norepinephrine in the a-receptor microenvironment is less than that placed in the organ bath, the appropriate comparison of pulmonary and femoral arterial response tol- norepinephrine stimulation requires uptake inhibition in both vessels. The concentration-response curve with uptake inhibition for the intralobar pulmonary artery is significantly to the left of that for the femoral; the -log EC50for the pulmonary vessel (6.63 ± 0.15) is greater than that of the femoral vessel (6.20 ± 0.13). The intralobar pulmonary artery in vitro is more sensitive tol-norepinephrine stimulation than is the femoral.