The action of adrenaline on the rat tail artery was similar to that of noradrenaline in that (i) adrenaline was more potent by the intraluminal than the extraluminal route of application, and (ii) cocaine eliminated the difference in potency by selectively enhancing the response to extraluminal adrenaline. In the absence of cocaine, extraluminal adrenaline was more potent than extraluminal noradrenaline; in the presence of cocaine, the two amines were equipotent, irrespective of the route of application. The intraluminal and extraluminal potencies of methoxamine did not differ, either in the absence or presence of cocaine. It is concluded that neuronal uptake is responsible for differences between the potencies of noradrenaline and adrenaline and for the effect of the route of applications on these potencies. Potentiation of responses to both noradrenaline and adrenaline by 27 µ M deoxycorticosterone acetate was minor compared with that by cocaine. The results provide further evidence that in the rat tail artery the extraneuronal uptake system is poorly developed compared with the neuronal uptake system.