Effects of uptake1 and uptake2 inhibition on the vasoconstrictor activity of noradrenaline (NA) in the perfused artery of the rabbit ear are reviewed in the light of data on NA metabolism and diffusion. 2. The minor effect of uptake1 inhibition on the response to intraluminal NA is related to location of the sympathetic nerves at the medial-adventitial border, and low diffusivity together with loss of amine by uptake2 in the media. 3. The minor effect of uptake2 inhibition on the vasoconstrictor activity of NA suggests that uptake2 has little effect on steady-state amine concentration in the media. This suggestion is supported by analyses of patterns of normetanephrine efflux from the artery. 4. Attention is drawn to the ability of uptake inhibitors, and of constriction and distension, to influence entry of NA into the artery wall.